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Journal articles on the topic 'Experimental arthriti'
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1
Gómez-SanMiguel, Ana Belén, Ana Isabel Martín, Maria Paz Nieto-Bona, Carmen Fernández-Galaz, María López-Menduiña, María Ángeles Villanúa, and Asunción López-Calderón. "Systemic α-melanocyte-stimulating hormone administration decreases arthritis-induced anorexia and muscle wasting." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 304, no. 10 (May 15, 2013): R877—R886. http://dx.doi.org/10.1152/ajpregu.00447.2012.
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Rheumatoid cachexia is associated with rheumatoid arthritis and it increases mortality and morbidity. Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that causes anorexia and muscle wasting. α-Melanocyte-stimulating hormone (α-MSH) has anti-inflammatory actions, and it is able to decrease inflammation in several inflammatory diseases including experimental arthritis. In this study we tested whether systemic α-MSH treatment is able to ameliorate cachexia in arthritic rats. On day 8 after adjuvant injection control and arthritic rats were treated with α-MSH (50 μg/rat ip) twice a day, until day 16 when all rats were euthanized. Arthritis decreased food intake, but it increased hypothalamic expression of neuropeptide Y (NPY) and Agouti-related peptides (AgRP) as well as interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) mRNA. In arthritic rats, α-MSH decreased the external signs of arthritis and increased food intake ( P < 0.01). In addition, α-MSH decreased hypothalamic expression of IL-1β, COX-2, proopiomelanocortin, and prohormone-converting (PC) enzymes PC1/3 and PC2 mRNA in arthritic rats. In control rats, α-MSH did not modify food intake or hypothalamic expression of aforementioned mRNA. α-MSH prevented arthritis-induced increase in gastrocnemius COX-2, muscle-specific RING-finger protein-1 (MuRF1), and atrogin-1 expression, and it increased fast myofiber size. In conclusion our data show that in arthritic rats peripheral α-MSH treatment has an anti-cachectic action increasing food intake and decreasing muscle wasting.
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Castillero, Estíbaliz, María Paz Nieto-Bona, Carmen Fernández-Galaz, Ana Isabel Martín, María López-Menduiña, Miriam Granado, María Angeles Villanúa, and Asunción López-Calderón. "Fenofibrate, a PPARα agonist, decreases atrogenes and myostatin expression and improves arthritis-induced skeletal muscle atrophy." American Journal of Physiology-Endocrinology and Metabolism 300, no. 5 (May 2011): E790—E799. http://dx.doi.org/10.1152/ajpendo.00590.2010.
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Arthritis is a chronic inflammatory illness that induces cachexia, which has a direct impact on morbidity and mortality. Fenofibrate, a selective PPARα activator prescribed to treat human dyslipidemia, has been reported to decrease inflammation in rheumatoid arthritis patients. The aim of this study was to elucidate whether fenofibrate is able to ameliorate skeletal muscle wasting in adjuvant-induced arthritis, an experimental model of rheumatoid arthritis. On day 4 after adjuvant injection, control and arthritic rats were treated with 300 mg/kg fenofibrate until day 15, when all rats were euthanized. Fenofibrate decreased external signs of arthritis and liver TNFα and blocked arthritis-induced decreased in PPARα expression in the gastrocnemius muscle. Arthritis decreased gastrocnemius weight, which results from a decrease in cross-section area and myofiber size, whereas fenofibrate administration to arthritic rats attenuated the decrease in both gastrocnemius weight and fast myofiber size. Fenofibrate treatment prevented arthritis-induced increase in atrogin-1 and MuRF1 expression in the gastrocnemius. Neither arthritis nor fenofibrate administration modify Akt-FoxO3 signaling. Myostatin expression was not modified by arthritis, but fenofibrate decreased myostatin expression in the gastrocnemius of arthritic rats. Arthritis increased muscle expression of MyoD, PCNA, and myogenin in the rats treated with vehicle but not in those treated with fenofibrate. The results indicate that, in experimental arthritis, fenofibrate decreases skeletal muscle atrophy through inhibition of the ubiquitin-proteasome system and myostatin.
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Perecko, Tomas, Katarina Drabikova, Antonin Lojek, Milan Ciz, Silvester Ponist, Katarina Bauerova, Radomir Nosal, Juraj Harmatha, and Viera Jancinova. "The Effects of Pterostilbene on Neutrophil Activity in Experimental Model of Arthritis." BioMed Research International 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/106041.
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It has been demonstrated that pterostilbene inhibits reactive oxygen species production in neutrophilsin vitro. However, little is known about its effects on neutrophils during inflammationin vivo. In this study, the effect of pterostilbene on neutrophil activity was investigated in experimental arthritis model. Lewis rats were injected by a single intradermal injection of heat-killedMycobacterium butyricumin Freund’s adjuvant to develop arthritis. Another group of arthritic animals received pterostilbene 30 mg/kg, daily, p.o. The number and activity of neutrophils in blood were measured on a weekly basis during the whole experiment. Moreover, the total radical trapping potential in plasma was measured at the end of the experiment. In the pterostilbene treated arthritic group, the treatment significantly lowered the number of neutrophils in blood on days 14 and 21 without significant downregulation of neutrophil oxidative burst. Pterostilbene nonsignificantly increased total radical trapping potential in arthritic animals. These results indicate that the promising effects of pterostilbene on reactive oxygen species operate by different mechanismsin vitroand in the animal model of inflammation. In conclusion, the positive effects of pterostilbene in the model of arthritis may be attributed to regulation of neutrophil number.
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LIU, XIUPING, ZHENGMING XIONG, SHEEN-WOO LEE, JELENA LEVI, SHAHRIAR YAGHOUBI, SANDIP BISWAL, SANJIV SAM GAMBHIR, and ZHEN CHENG. "A NEAR-INFRARED FLUORESCENT DEOXYGLUCOSE DERIVATIVE FOR OPTICAL IMAGING OF EXPERIMENTAL ARTHRITIS." Journal of Innovative Optical Health Sciences 02, no. 02 (April 2009): 179–87. http://dx.doi.org/10.1142/s1793545809000450.
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The purpose of this study is to investigate whether a near-infrared fluorescence (NIRF) probe, Cy5.5-D-glucosamine (Cy5.5-2DG), can image arthritis in collagen-induced arthritic (CIA) mice. The presence of arthritis was verified by both visual examination and micro-computed tomography (MicroCT) imaging. CIA mice were imaged by a micro-positron emission tomography (MicroPET) scanner one hour after intravenous injection of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). After radioactivity of [18F]FDG decayed away, Cy5.5-2DG was injected into a lateral tail vein of the mice. Arthritic tissue targeting and retention of Cy5.5-2DG in CIA mice were evaluated and quantified by an optical imaging system. Inflammatory tissue in CIA mice was clearly visualized by [18F]FDG-MicroPET scan. NIRF imaging of Cy5.5-2DG in the same mice revealed that the pattern of localization of Cy5.5-2DG in the arthritic tissue was very similar to that of [18F]FDG. Quantification analysis further showed that [18F]FDG uptake in arthritic tissues at one hour post-injection (p.i.) and Cy5.5-2DG uptakes at different time points p.i. were all well correlated (r2over 0.65). In conclusion, Cy5.5-DG can detect arthritic tissues in living mice. The good correlation between the [18F]FDG uptake and Cy5.5-2DG accumulation in the same arthritic tissue warrants further investigation of Cy5.5-2DG as an approach for assessment of anti-inflammatory treatments.
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Brown, Charles R., and Steven L. Reiner. "Clearance of Borrelia burgdorferi May Not Be Required for Resistance to Experimental Lyme Arthritis." Infection and Immunity 66, no. 5 (May 1, 1998): 2065–71. http://dx.doi.org/10.1128/iai.66.5.2065-2071.1998.
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ABSTRACT Infection of inbred mouse strains with Borrelia burgdorferi results in the development of experimental Lyme arthritis. The degree of arthritic pathology has been suggested to correlate with the level of spirochete burden within tissues. To investigate this further, we infected resistant DBA/2 (DBA) and susceptible C3H/HeJ (C3H) mice in the hind footpads and monitored arthritis development for 21 days. To quantitate levels of spirochetes within tissues, we created a competitive PCR molecule containing modified ospA and fla gene segments. C3H mice developed severe arthritis of the tibiotarsal joints, while DBA mice developed only mild inflammation throughout the experimental period. At day 21, when the gross size and histologic composition of ankles revealed significant differences in arthritis between the strains, there was little difference in levels of spirochete DNA as determined by competitive PCR. Cultures of ankle tissue at day 21 were also uniformly positive in both C3H and DBA animals and contained relatively similar levels of spirochetes. These results indicate that the presence of spirochetes in the ankles of experimental animals is not sufficient for arthritis development. Since arthritic and nonarthritic animals can harbor relatively equal spirochete burdens yet retain their distinct phenotypic outcomes, an aberrant or overly exuberant immune response may be an additional requirement for pathology in arthritis-prone mice.
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Fernandes, E. S., S. Awal, R. Karadaghi, and S. D. Brain. "TRP Receptors in Arthritis, Gaining Knowledge for Translation from Experimental Models." Open Pain Journal 6, no. 1 (March 8, 2013): 50–61. http://dx.doi.org/10.2174/1876386301306010050.
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Arthritis is a condition characterised by mainly pain, reduced joint movement and signs of inflammation, such as swelling. The disorder has many different types, of which osteoarthritis (a degenerative joint disease) and rheumatoid arthritis (a chronic autoimmune disease) are the two most common forms. There are >6 million sufferers in the UK and both conditions have a huge potential to impair capabilities and contribute to social and economic burdens. Whilst there are a wide range of arthritic therapies available, many patients under treatment complain of poor pain relief. Thus there is a need for novel therapeutic approaches, and the transient receptor potential (TRP) family of receptor channels has been investigated. One particular area of recent research has been the ligand-gated transient receptor potential vanilloid 1 (TRPV1) channel. Findings from numerous pre-clinical models and scientific studies have shown that TRPV1 desensitisation, or the use of TRPV1 antagonists alleviates pain and some inflammatory aspects. New findings have started to unveil the potential of other TRP channels in mediating arthritic pain and inflammation. With the understanding that the currently available treatments for arthritis are limited, researchers have looked into the exciting prospect that TRP receptor antagonists may be developed into effective, specific drugs, which would potentially protect against the complications of arthritis. These antagonists are still under development, although only data from studies from pre-clinical models are currently available. This review acts to summarize knowledge of the potential influence of TRP receptors in arthritis to date.
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Gómez-SanMiguel, Ana Belén, Carolina Gomez-Moreira, María Paz Nieto-Bona, Carmen Fernández-Galaz, Maria Ángeles Villanúa, Ana Isabel Martín, and Asunción López-Calderón. "Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis." American Journal of Physiology-Endocrinology and Metabolism 310, no. 11 (June 1, 2016): E925—E937. http://dx.doi.org/10.1152/ajpendo.00503.2015.
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Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. β2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective β2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected daily with 50 μg/kg sc formoterol or saline for 12 days. Body weight change, food intake, and arthritis index were analyzed. After euthanasia, in the gastrocnemius mRNA was analyzed by PCR, and proteins were analyzed by Western blotting. Arthritis decreased gastrocnemius weight, cross-sectional area, and myofiber size, whereas formoterol increased those variables in both arthritic and control rats. Formoterol decreased the external signs of arthritis as well as NF-κB(p65) activation, TNFα, and COX-2 levels in the gastrocnemius of arthritic and control rats. Those effects of formoterol were associated with a decreased expression of myostatin, atrogin-1, and MuRF1 and in LC3b lipidation. Arthritis increased the expression of MyoD, myogenin, IGF-I, and IGFBP-3 and -5 in the gastrocnemius. In control and in arthritic rats, treatment with formoterol increased Akt phosphorylation and myogenin levels, whereas it decreased IGFBP-3 expression in the gastrocnemius. These data suggest that formoterol has an anti-inflammatory effect and decreases muscle wasting in arthritic rats through increasing Akt activity and myogenin and decreasing myostatin, the p-NF-κB(p65)/TNF pathway, and IGFBP-3.
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Granado, Miriam, Ana I. Martín, Mª Ángeles Villanúa, and Asunción López-Calderón. "Experimental arthritis inhibits the insulin-like growth factor-I axis and induces muscle wasting through cyclooxygenase-2 activation." American Journal of Physiology-Endocrinology and Metabolism 292, no. 6 (June 2007): E1656—E1665. http://dx.doi.org/10.1152/ajpendo.00502.2006.
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Chronic arthritis induces cachexia associated with an inhibition of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) system and an activation of the E3 ubiquitin-ligating enzymes muscle atrophy F-box (MAFbx) and muscle Ring finger 1 (MuRF1) in the skeletal muscle. The aim of this work was to study the role of cyclooxygenase (COX)-2 in chronic arthritis-induced cachexia. Arthritis was induced in rats by Freund's adjuvant injection, and the effects of two COX inhibitors (indomethacin, a nonspecific inhibitor, and meloxicam, a selective COX-2 inhibitor on pituitary GH and on liver and serum IGF-I levels) were tested. Arthritis decreased body weight gain and GH and liver IGF-I gene expression. In the arthritic rats, both inhibitors, indomethacin and meloxicam, prevented the inhibitory effect of arthritis on body weight gain. Indomethacin and meloxicam administration to arthritic rats increased pituitary GH and liver IGF-I mRNA as well as serum levels of IGF-I. These data suggest that induction of COX-2 during chronic inflammation is involved in the inhibition of the GH-IGF-I axis and in the body weight loss. In the gastrocnemius muscle, arthritis increased the gene expression of tumor necrosis factor (TNF)-α, the E3 ubiquitin-ligating enzymes MAFbx and MuRF1, as well as of IGF-I and IGF-binding protein-5 (IGFBP-5). Inhibition of COX-2 by meloxicam administration increased gastrocnemius weight and decreased MAFbx, MuRF1, TNF-α, and IGFBP-5 gene expression. In summary, our data indicate that chronic arthritis-induced cachexia and muscle wasting are mediated by the COX-2 pathway resulting in a decreased GH-IGF-I secretion and increased expression of MAFbx and MuRF1 mRNA.
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Dorst, Daphne N., Mark Rijpkema, Marti Boss, Birgitte Walgreen, Monique M. A. Helsen, Desirée L. Bos, Maarten Brom, et al. "Targeted photodynamic therapy selectively kills activated fibroblasts in experimental arthritis." Rheumatology 59, no. 12 (July 30, 2020): 3952–60. http://dx.doi.org/10.1093/rheumatology/keaa295.
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Abstract Objective In RA, synovial fibroblasts become activated. These cells express fibroblast activation protein (FAP) and contribute to the pathogenesis by producing cytokines, chemokines and proteases. Selective depletion in inflamed joints could therefore constitute a viable treatment option. To this end, we developed and tested a new therapeutic strategy based on the selective destruction of FAP-positive cells by targeted photodynamic therapy (tPDT) using the anti-FAP antibody 28H1 coupled to the photosensitizer IRDye700DX. Methods After conjugation of IRDye700DX to 28H1, the immunoreactive binding and specificity of the conjugate were determined. Subsequently, tPDT efficiency was established in vitro using a 3T3 cell line stably transfected with FAP. The biodistribution of [111In]In-DTPA-28H1 with and without IRDye700DX was assessed in healthy C57BL/6N mice and in C57BL/6N mice with antigen-induced arthritis. The potential of FAP-tPDT to induce targeted damage was determined ex vivo by treating knee joints from C57BL/6N mice with antigen-induced arthritis 24 h after injection of the conjugate. Finally, the effect of FAP-tPDT on arthritis development was determined in mice with collagen-induced arthritis. Results 28H1-700DX was able to efficiently induce FAP-specific cell death in vitro. Accumulation of the anti-FAP antibody in arthritic knee joints was not affected by conjugation with the photosensitizer. Arthritis development was moderately delayed in mice with collagen-induced arthritis after FAP-tPDT. Conclusion Here we demonstrate the feasibility of tPDT to selectively target and kill FAP-positive fibroblasts in vitro and modulate arthritis in vivo using a mouse model of RA. This approach may have therapeutic potential in (refractory) arthritis.
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Dorst, Daphne N., Marti Boss, Mark Rijpkema, Birgitte Walgreen, Monique M. A. Helsen, Desirée L. Bos, Louis van Bloois, et al. "Photodynamic Therapy Targeting Macrophages Using IRDye700DX-Liposomes Decreases Experimental Arthritis Development." Pharmaceutics 13, no. 11 (November 5, 2021): 1868. http://dx.doi.org/10.3390/pharmaceutics13111868.
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Macrophages play a crucial role in the initiation and progression of rheumatoid arthritis (RA). Liposomes can be used to deliver therapeutics to macrophages by exploiting their phagocytic ability. However, since macrophages serve as the immune system’s first responders, it is inadvisable to systemically deplete these cells. By loading the liposomes with the photosensitizer IRDye700DX, we have developed and tested a novel way to perform photodynamic therapy (PDT) on macrophages in inflamed joints. PEGylated liposomes were created using the film method and post-inserted with micelles containing IRDye700DX. For radiolabeling, a chelator was also incorporated. RAW 264.7 cells were incubated with liposomes with or without IRDye700DX and exposed to 689 nm light. Viability was determined using CellTiterGlo. Subsequently, biodistribution and PDT studies were performed on mice with collagen-induced arthritis (CIA). PDT using IRDye700DX-loaded liposomes efficiently induced cell death in vitro, whilst no cell death was observed using the control liposomes. Biodistribution of the two compounds in CIA mice was comparable with excellent correlation of the uptake with macroscopic and microscopic arthritis scores. Treatment with 700DX-loaded liposomes significantly delayed arthritis development. Here we have shown the proof-of-principle of performing PDT in arthritic joints using IRDye700DX-loaded liposomes, allowing locoregional treatment of arthritis.
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Dudics, Steven, Shivaprasad Venkatesha, and Kamal Moudgil. "The Micro-RNA Expression Profiles of Autoimmune Arthritis Reveal Novel Biomarkers of the Disease and Therapeutic Response." International Journal of Molecular Sciences 19, no. 8 (August 5, 2018): 2293. http://dx.doi.org/10.3390/ijms19082293.
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Rheumatoid arthritis (RA) is a chronic autoimmune disease of the joints affecting about 0.3–1% of the population in different countries. About 50–60 percent of RA patients respond to presently used drugs. Moreover, the current biomarkers for RA have inherent limitations. Consequently, there is a need for additional, new biomarkers for monitoring disease activity and responsiveness to therapy of RA patients. We examined the micro-RNA (miRNA) profile of immune (lymphoid) cells of arthritic Lewis rats and arthritic rats treated with celastrol, a natural triterpenoid. Experimental and bioinformatics analyses revealed 8 miRNAs (miR-22, miR-27a, miR-96, miR-142, miR-223, miR-296, miR-298, and miR-451) and their target genes in functional pathways important for RA pathogenesis. Interestingly, 6 of them (miR-22, miR-27a, miR-96, miR-142, miR-223, and miR-296) were further modulated by celastrol treatment. Interestingly, serum levels of miR-142, miR-155, and miR-223 were higher in arthritic versus control rats, whereas miR-212 showed increased expression in celastrol-treated rats compared with arthritic rats or control rats. This is the first study on comprehensive miRNA expression profiling in the adjuvant-induced arthritis (AA) model and it also has revealed new miRNA targets for celastrol in arthritis. We suggest that subsets of the above miRNAs may serve as novel biomarkers of disease activity and therapeutic response in arthritis.
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Sadalage, Nikita A., Nayeem A. Khatib, Sunil S. Jalalpure, Shrinivas Patil, and Mrityunjaya B. Ullagaddi. "Ventoluft Polyherbal formulation modulates Freund’s Complete Adjuvant induced arthritis in experimental rats." International Journal of Ayurvedic Medicine 12, no. 3 (September 29, 2021): 523–28. http://dx.doi.org/10.47552/ijam.v12i3.2132.
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Background: Ventoluft Polyherbal formulation composes multiple traditional medicinal plants composed of various anti-inflammatory agents. Hence, the present study aimed to investigate the effect of Ventoluft Polyherbal formulation on Freund’s complete adjuvant-induced arthritic male Wistar rats. Materials and methods: The study included thirty-six rats, containing six in each. Arthritis was induced by injecting FCA (0.1ml) in joints of the right sub-plantar region of rats in negative control and all test groups i.e. (20, 40, and 80mg/kg p.o) for 28 days except normal group. A positive control, indomethacin (10mg/kg, i.p.) was also tested for 28 days. During the treatment, paw volume was measured weekly once. At the end of the experiment, physical, hematological, and biochemical effects were evaluated. Results:Administration of Ventoluft at the doses of 20, 40, and 80 mg/kg b.w. p.o exhibited statistically significant (p < 0.001) inhibition of the paw edema and joint swelling, along with an increase in body weight, decrease in rheumatoid and spleen index factors. Conclusion: The results from hematological and biochemical parameters have shown that Ventoluft possesses potent anti-arthritic activity, Results obtained in the present study indicate that Ventoluft formulation has exhibited, dose-dependent improvement in FCA induced rheumatoid arthritis.
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Ishikawa, Larissa Lumi Watanabe, Priscila Maria Colavite, Larissa Camargo da Rosa, Bianca Balbino, Thais Graziela Donegá França, Sofia Fernanda Gonçalves Zorzella-Pezavento, Fernanda Chiuso-Minicucci, and Alexandrina Sartori. "Commercial Bovine Proteoglycan Is Highly Arthritogenic and Can Be Used as an Alternative Antigen Source for PGIA Model." BioMed Research International 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/148594.
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Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. It affects mainly the joints, causing synovitis, cartilage destruction, and bone erosion. Many experimental models are used to study the mechanisms involved in immunopathogenesis and new therapies for this disease. Proteoglycan-induced arthritis (PGIA) is a widely used model based on the cross-reactivity of injected foreign (usually human) PG and mice self-PG. Considering the complexity of the extraction and purification of human PG, in this study we evaluated the arthritogenicity of bovine PG that is commercially available. Bovine PG was highly arthritogenic, triggering 100% incidence of arthritis in female BALB/c retired breeder mice. Animals immunized with bovine PG presented clinical symptoms and histopathological features similar to human RA and other experimental models. Moreover, bovine PG immunization determined higher levels of proinflammatory and anti-inflammatory cytokines in arthritic mice compared to healthy ones. As expected, only the arthritic group produced IgG1 and IgG2a antibodies against PG. Thus, commercial bovine PG can be used as an alternative antigenic source to PGIA for the study of many RA aspects, including the immunopathogenesis of the disease and also the development of new therapies.
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Chen, Xi, Cheng Yi Zhang, and Hao Gang Xue. "Effect of Arthrigia on Adjuvant Arthritis Rats’ IL-12." Applied Mechanics and Materials 140 (November 2011): 43–47. http://dx.doi.org/10.4028/www.scientific.net/amm.140.43.
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Rheumatoid Arthritis （RA） is a systemic chronic autoimmune disease. To study the therapeutic mechanism of effects of Skullcap Brightviolet （SB），glucosamine/chondroitin （GC），and the combination of them (named Arthrigia) on RA. With the adjuvant arthritis (AA) rat models, we observed the protective effects of oral SB, GC and Arthrigia in different concentrations on AA in rats. We further examined the immunological mechanism of the combination of them by testing the rats’ secretion of IL-12. The results showed that Arthrigia inhibited the production and secretion of IL-12 factors in some extent, and its effects are more potent the single SB or GC. The present study provides the experimental evidences for Arthrigia for its further development, clinical prevention and treatment of RA.
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Perruche, Sylvain, Amandine Clauzon, Francis Bonnefoy, and Philippe Saas. "Apoptotic cell-based therapy to treat collagen-induced experimental arthritis (P5191)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 68.23. http://dx.doi.org/10.4049/jimmunol.190.supp.68.23.
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Abstract Biotherapies are emerging to treat rheumatoid arthritis (RA). Most of them target a cellular or soluble factor involved in the physiopathology of RA. Here we evaluated whether immunomodulatory properties of apoptotic cells can treat RA. Apoptotic cell approach has been successfully assessed to prevent arthritis development in experimental rat model, as well as in other inflammatory experimental settings. Thus we investigated apoptotic cell injection to treat RA in a mouse model of collagen-induced arthritis (CIA). Four to 8 days after CIA development in susceptible DBA/1, mice presenting arthritic symptoms were treated with apoptotic cells (5.10e6 cell/mouse). As control, methotrexate was used (MTX, 15 mg/kg, twice) alone or with apoptotic cells. Regulatory T cells (Treg) were assessed by FACS at time of sacrifice (day 40/45). Apoptotic cell injection demonstrated a significant decrease of arthritis score (p>0.01; 4 independent experiments), associated with an increased percentage of Treg in the spleen at time of sacrifice. MTX was sufficient to decrease arthritis as well and apoptotic cell injection did not influence MTX efficiency and vice-et-versa. Whereas MTX did not affect the percentage of Treg, MTX + apoptotic cell treatment induced a strong increase of Treg in the spleen and draining lymph nodes. Apoptotic cell injection is an effective treatment to reduce RA severity and should be consider in clinic as an alternative method for biotherapy refractory patients.
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Ramez, Mohamed, Toni Forde, Chi-Wing Chow, and Vyacheslav Adarichev. "Genome-wide association study of inbred murine strains discovered nuclear factor of activated T-cells Nfatc4 as a major gene controlling severity of inflammatory arthritis. (47.14)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 47.14. http://dx.doi.org/10.4049/jimmunol.186.supp.47.14.
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Abstract Nuclear factor of activated T cells (NFAT) is a family of transcription factors critical in regulating gene expression in development and disease. NFAT is an important target for cyclosporine immunosuppression in transplant rejection. The NFAT pathway is also important in inflammatory and autoimmune diseases such as rheumatoid arthritis. Using genome-wide association study (GWAS) of antibody-mediated arthritis in inbred murine strains, we found NFATc4 within the major arthritis severity peak at 56.35-56.46 Mb of chromosome 14 with genetic association of log(1/p) > 5.5. To confirm the genetic linkage and functional significance of the NFATc4 gene, we performed collagen antibody-induced arthritis (CAIA) and found that NFATc4-deficient mice exhibited significantly reduced inflammation as compared to wild-type counterparts (55% downregulation, p < 0.01). Immunoblotting analysis demonstrated the presence of NFATc4 in articular cartilage and chondrocytes derived from femoral heads of arthritic and naïve mice. Notably, NFATc4 in chondrocytes isolated from arthritic mice was hypo-phosphorylated as compared to naïve cells, indicating activation of NFATc4. NFATc4, as expected, was not found in splenocytes. We also performed genome-wide Affymetrix oligonucleotide array studies in CAIA experimental arthritis model using wild type and NFATc4-deficient mice. Taking together, we uncovered a novel role of NFATc4 in inflammatory arthritis in chondrocytes.
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BLOEMENDAL, A., R. VAN DER ZEE, V. P. M. G. RUTTEN, P. J. S. VAN KOOTEN, J. C. FARINE, and W. VAN EDEN. "Experimental immunization with anti-rheumatic bacterial extract OM-89 induces T cell responses to heat shock protein (hsp)60 and hsp70; modulation of peripheral immunological tolerance as its possible mode of action in the treatment of rheumatoid arthriti." Clinical & Experimental Immunology 110, no. 1 (September 1997): 72–78. http://dx.doi.org/10.1111/j.1365-2249.1997.484-ce1378.x.
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Gözel, Nevzat. "Sorafenib Reveals Anti-Arthritic Potentials in Collagen Induced Experimental Arthritis Model." Archives of Rheumatology 33, no. 3 (September 5, 2018): 309–15. http://dx.doi.org/10.5606/archrheumatol.2018.6652.
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Grespan, Renata, Marcia Paludo, Henrique de Paula Lemos, Carmem Patr^ ^iacute;cia Barbosa, Ciomar Aparecida Bersani-Amado, Marcia Machado de Oliveira Dalalio, and Roberto Kenji Nakamura Cuman. "Anti-arthritic Effect of Eugenol on Collagen-Induced Arthritis Experimental Model." Biological and Pharmaceutical Bulletin 35, no. 10 (2012): 1818–20. http://dx.doi.org/10.1248/bpb.b12-00128.
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Baroroh, Hanif Nasiatul, Esti Dyah Utami, and Anisyah Achmad. "Psidium guajava leaves decrease arthritic symptoms in adjuvant-induced arthritic rats." Universa Medicina 34, no. 3 (April 27, 2016): 197. http://dx.doi.org/10.18051/univmed.2015.v34.197-204.
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BACKGROUND <br />Guava is an herbal with proven antioxidant and anti-inflammatory properties. The aim of this study was to investigate the anti-arthritic activity of the ethanol extract of Psidium gujava leaves (EEPG) against complete Freund’s adjuvant (CFA) induced arthritis in rats. <br /><br />METHODS<br />An experimental study was conducted on 40 male Wistar Sprague Dawley rats, which were divided into 5 groups. Each group was induced with 0.2 mL CFA (1 mg/mL) on day 1 and 0.1 CFA mL booster injection on day 5. Group I served as an arthritic control, group II received dexamethasone (6.75 mg.kg-1 orally), group III, IV and V received EEPG at oral doses of 250, 500, and 750 mg/kg BW, respectively, on days 14 to 28. Anti-arthritic activity was observed from the arthritis score, the paw circumference was measured on days 0, 1, 4, 8, 12, 16, 20, 24, and 28, the mobility score was determined on days 12 and 28, and the histolopathology of the knee joint was examined on day 29. <br /><br />RESULTS<br />Ethanol extract of Psidium guajava leaves significantly suppressed the swelling of the paws in chronic phase based on increasing of edema (%), while starting on day 20. EEPG at 250 mg/kg was most effective in significantly reducing arthritis scores (p<0.05). Histopathological examination showed repair of the knee joint synovial membrane and cartilage.<br /> <br />CONCLUSIONS<br />Psidium guajava leaf extract is effective in decreasing the inflammatory response and arthritic symptoms in rats with adjuvant-induced arthritis. Psidium guajava leaves can be developed into an alternative anti-arthritis treatment.
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Morsoleto, Felipe Misael da Silva, Pedro Rondon Werneck, Fernando Russo Costa do Bomfim, and Maria Jose Misael da Silva Morsoleto. "Ultrasound wave transports apitoxin in arthritic joint. - Experimental study." Research, Society and Development 11, no. 7 (June 3, 2022): e53311730386. http://dx.doi.org/10.33448/rsd-v11i7.30386.
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Man, in his common lore started using the toxin produced by bees, apitoxin, as a topical medication for rheumatoid arthritis in time immemorial. Systematically subjecting themselves to bee stings. In this study, we sought to use this substance, apitoxin, in an experimental model of induced arthritis. In order for the substance to be introduced through the tissue, ultrasound was used as a vehicle, this action is called phonophoresis. So that the apitoxin would reach the arthritic joint. Wistar rats were used in a model where arthritis was induced by inoculation into the knee joint with zymosan. The animals were divided into groups: GI (positive control), GII (negative control), GIII (topical apitoxin-treated group), GIV (ultrasound-treated group) and GV (phonophoresis-treated group). Inducing arthritis, once established, treatment of the groups was initiated. After 21 days of treatment, the animals were anesthetized with ketamine and xylazine, their knees were submitted to radiographic images, temperatures were collected and euthanized. The RX films were processed by Image J software to collect the intra-articular distance of the femur and tibia. The temperature of each individual in the group was collected. Space and temperature averages: Group I (0.15 mm and 35.7°C), group II (0.03 mm and 38.2°C), group III, (0.4 mm and 37.8°C), group IV (0.6 mm and 36.7°C) to group V (0.78 mm and 36.2°C). We conclude that ultrasound combined with apitoxin via phonophoresis was efficient in tissue repair and subsequent regeneration of joint contours when compared with ultrasound or topical apitoxin alone.
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Uroos, Maliha, Zaigham Abbas, Shumaila Sattar, Nigarish Umer, Arham Shabbir, Shafiq-ur-Rehman, and Ahsan Sharif. "Nyctanthes arbor-tristisAmeliorated FCA-Induced Experimental Arthritis: A Comparative Study among Different Extracts." Evidence-Based Complementary and Alternative Medicine 2017 (2017): 1–13. http://dx.doi.org/10.1155/2017/4634853.
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Nyctanthes arbor-tristis(NAT) is commonly used traditionally for the treatment of rheumatism and inflammatory diseases. Current study evaluates the antiarthritic potential of NAT using Freund’s adjuvant-induced arthritic rat model. Treatments with methanolic, ethyl acetate, and n-hexane extracts were continued for consecutive 20 days. Macroscopic arthritic scoring and water displacement plethysmometry were used to evaluate arthritic development. Hematological and biochemical parameters were investigated and ankle joints were processed for histopathological evaluation. Qualitative phytochemical analysis and GC-MS analysis were conducted for identification of constituents. NAT extracts suppressed arthritic scoring, paw edema, infiltration of inflammatory cells, pannus formation, and bone erosion. The plant extracts ameliorated total leukocytes and platelet counts and nearly normalized red blood cells (RBC) counts and hemoglobin (Hb) content. The extracts were found safe in terms of hepatotoxicity and nephrotoxicity as determined by aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea levels. Comparative analysis showed that ethyl acetate extract produced the highest inhibition of paw edema. The major constituents found in ethyl acetate extract can be classified into three major classes, that is, terpenes, terpenoids, fatty acids, and iridoid glycosides. Current study showed thatNyctanthes arbor-tristisameliorated experimental rheumatoid arthritis and ethyl acetate extract possessed the highest inhibitory activity.
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Xiaoming, Donghui Guo, Jianyong Zhao, Xing, Hengjun Wang, Shiqiang, Yunchao Zhao, and Xinlong. "Fisetin Attenuates Cartilage Destruction in Adjuvant-Induced Arthritis by Modulating Cartilage Cytokine Expression Correlated with Oxidative Status in the Early Phase in Experimental Animals." Folia Biologica 67, no. 4 (December 31, 2019): 177–89. http://dx.doi.org/10.3409/fb_67-4.18.
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The present study was designed to evaluate the effect of Fisetin on the progression of adjuvant-induced arthritis in rats and explore the mechanisms underlying fisetin mediated immunomodulation. Adjuvant-induced arthritis (AIA) was induced by a single subcutaneous injection of Freund's complete adjuvant (FCA). AIA rats were treated with Fisetin daily via oral gavage, for a period of 28 days. Paw swelling changes were assessed and histopathological and radiographic analysis was conducted to evaluate the antiarthritic effect. Lipid peroxidation and antioxidant enzyme activities in the joint tissue homogenate were performed to observe the modulation of the antioxidant status along the expression of different pro-inflammatory cartilage cytokines, such as TNF-á and IL-6. Fisetin promotes both the antiarthritic and the antioxidant effect, as well as the suppression of lipid peroxidation. Fisetin significantly inhibited the development phase of arthritis, as supported by histopathological and radiographical observations, and reduced overexpression of cartilage cytokines. Fisetin not only suppressed the arthritic progression and tissue destruction, but it also demonstrated a pronounced anti-inflammatory and immunomodulatory action against the immunosuppressive properties of AIA and provided a superior effect against inflammation. Furthermore, fisetin therapy restored the BMD loss and acts as a potent antioxidant and immunomodulator, suggesting that oral administration can suppress arthritic progression in rats.
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Ponist, S., F. Drafi, V. Kuncirova, D. Mihalova, L. Rackova, L. Danisovic, O. Ondrejickova, et al. "Effect of Carnosine in Experimental Arthritis and on Primary Culture Chondrocytes." Oxidative Medicine and Cellular Longevity 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/8470589.
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Carnosine’s (CARN) anti-inflammatory potential in autoimmune diseases has been but scarcely investigated as yet. The aim of this study was to evaluate the therapeutic potential of CARN in rat adjuvant arthritis, in the model of carrageenan induced hind paw edema (CARA), and also in primary culture of chondrocytes under H2O2injury. The experiments were done on healthy animals, arthritic animals, and arthritic animals with oral administration of CARN in a daily dose of 150 mg/kg b.w. during 28 days as well as animals with CARA treated by a single administration of CARN in the same dose. CARN beneficially affected hind paw volume and changes in body weight on day 14 and reduced hind paw swelling in CARA. Markers of oxidative stress in plasma and brain (malondialdehyde, 4-hydroxynonenal, protein carbonyls, and lag time of lipid peroxidation) and also activity of gamma-glutamyltransferase were significantly corrected by CARN. CARN also reduced IL-1alpha in plasma. Suppression of intracellular oxidant levels was also observed in chondrocytes pretreated with CARN. Our results obtained on two animal models showed that CARN has systemic anti-inflammatory activity and protected rat brain and chondrocytes from oxidative stress. This finding suggests that CARN might be beneficial for treatment of arthritic diseases.
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Pašková, Ľudmila, Viera Kuncírová, Silvester Poništ, Danica Mihálová, Radomír Nosáľ, Juraj Harmatha, Iveta Hrádková, et al. "Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver." Journal of Immunology Research 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/7509653.
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Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-αand iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1βin plasma and IL-1βmRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX.
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Wang, Ting-Yu, Jun Li, Jin-Fang Ge, Chang-Yu Li, Yong Jin, Xiong-Wen Lü, Wen-Ming Cheng, and Ji-Hui Tang. "Preliminary Study of Total Flavonoids fromLitsea coreanaLevl. on Experimental Adjuvant-Induced Arthritis in Rats." American Journal of Chinese Medicine 36, no. 05 (January 2008): 899–912. http://dx.doi.org/10.1142/s0192415x08006338.
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Litsea coreana Levl., a traditional Chinese medicine, has long been used for its diverse benefits such as detoxification and detumescence. Total flavonoids from Litsea coreana Levl. (TFLC) are the effective fraction of L. coreana. This study was designed to investigate the anti-inflammatory effects and mechanisms of TFLC against Feund's complete adjuvant (FCA)-induced arthritis in rats. Arthritis was evaluated by secondary paw swelling, polyarthritis index, body weight and histopathologic analysis. Con A- or LPS-stimulated splenocyte proliferation and cytokine (IL-1 and IL-2) production were assessed by MTT assay and activated mouse cell proliferation assay, respectively. The results indicate that therapeutic administration of TFLC (50, 100, 200 mg/kg, ig × 12 days ) could significantly suppress secondary arthritis in rats with adjuvant-induced arthritis (AA). In vivo, TFLC (50, 100, 200 mg/kg, ig × 12 days ) augmented splenocyte proliferation and increased IL-2 production in splenocytes, while reduced IL-1 activity in peritoneal macrophages (PMΦ) of AA rats. In vitro, TFLC at concentrations from 0.005 to 50 μg/ml exerted the same immunoregulatory effects on AA rats as those in vivo. In addition, an attractive feature of TFLC lies in its apparent lack of toxicity. These results suggest that TFLC without toxicity has a significant anti-arthritic effect on AA rats which could be associated with its anti-inflammatory and immunomodulatory properties.
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Planck, Stephen R., April Woods, Jenna S. Clowers, Martin J. Nicklin, James T. Rosenbaum, and Holly L. Rosenzweig. "Impact of IL-1 signalling on experimental uveitis and arthritis." Annals of the Rheumatic Diseases 71, no. 5 (January 20, 2012): 753–60. http://dx.doi.org/10.1136/annrheumdis-2011-200556.
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BackgroundUveitis, or inflammatory eye disease, is a common extra-articular manifestation of many systemic autoinflammatory diseases involving the joints. Anakinra (recombinant interleukin (IL)-1 receptor antagonist (Ra)) is an effective therapy in several arthritic diseases; yet, few studies have investigated the extent to which IL-1 signalling or IL-1Ra influences the onset and/or severity of uveitis.ObjectiveTo seek possible links between arthritis and uveitis pathogenesis related to IL-1 signalling.MethodsThe eyes of IL-1Ra-deficient BALB/c mice were monitored histologically and by intravital videomicroscopy to determine if uveitis developed along with the expected spontaneous arthritis in ankles and knees. Expression levels of IL-1R and its negative regulators (IL-1Ra, IL-1RII, IL-1RAcP and single Ig IL-1R-related molecule) in eye and joint tissues were compared. Differences in uveitis induced by intraocular injection of lipopolysaccharide (LPS) in mice lacking IL-1R or IL-1Ra were assessed.ResultsDeficiency in IL-1Ra predisposes to spontaneous arthritis, which is exacerbated by previous systemic LPS exposure. The eye, however, does not develop inflammatory disease despite the progressive arthritis or LPS exposure. Organ-specific expression patterns for IL-1Ra and negative regulators of IL-1 activity were observed that appear to predict predisposition to inflammation in each location in IL-1Ra knockout mice. The eye is extremely sensitive to locally administered LPS, and IL-1Ra deficiency markedly exacerbates the resulting uveitis.ConclusionThis study demonstrates that IL-1Ra plays an important role in suppressing local responses in eyes injected with LPS and that there is discordance between murine eyes and joints in the extent to which IL-1Ra protects against spontaneous inflammation.
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Shahin, Dina, Ehab El Toraby, Hala Abdel-Malek, Vivian Boshra, Ayman Z. Elsamanoudy, and Dalia Shaheen. "Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonist (Pioglitazone) and Methotrexate on Disease Activity in Rheumatoid Arthritis (Experimental and Clinical Study)." Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders 4 (January 2011): CMAMD.S5951. http://dx.doi.org/10.4137/cmamd.s5951.
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Objective To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical. Methods Experimentally: 50 rats were divided into 5 equal groups; controls, experimental arthritis, methorexate treated (0.1 mg/Kg daily), pioglitazone-treated (10 mg/kg daily), and methotrexate and pioglitazone treated. Clinically: forty-nine diabetic rheumatoid arthritis patients were included. Patients group consisted of 28 patients and they received pioglitazone 30 mg orally beside their usual treatment. Control group consisted of 21 patients and they continued their usual treatment plus placebo. Disease activity was assessed using DAS28 score. Patients were followed up for 3 months. Results Pioglitazone produced a significant improvement of serum oxidative stress parameters ( P < 0.05), and inflammatory cytokines in the treated arthritic group ( P < 0.05). Clinically, the pioglitazone treated group showed significant improvement in DAS28 ( P = 0.001) and C-reactive protein ( P < 0.0001) compared to placebo group. Conclusion The concomitant use of the PPAR γ agonist pioglitazone and methotrexate appears to be promising therapeutic strategy for rheumatoid arthritis patients.
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Beckmann, Nadine, Katrin Anne Becker, Silke Walter, Jan U. Becker, Melanie Kramer, Gabriele Hessler, Stefanie Weber, et al. "Regulation of Arthritis Severity by the Acid Sphingomyelinase." Cellular Physiology and Biochemistry 43, no. 4 (2017): 1460–71. http://dx.doi.org/10.1159/000481968.
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Background/Aims: Rheumatoid arthritis is a chronic autoimmune disease hallmarked by inflammation in synovial joints. Treatment is hampered by the lack of a cure and current disease-modifying drugs are associated with potentially severe toxicities. Methods: We investigated arthritis severity by measuring joint swelling and pro-inflammatory cytokine production in a murine experimental model of inflammatory arthritis (antigen-induced arthritis). We analyzed acid sphingomyelinase knock-out mice and wild-type littermates, as well as mice treated with the pharmacological acid sphingomyelinase inhibitor amitriptyline. Results: Genetic ablation or pharmacological inhibition of acid sphingomyelinase reduced joint swelling and levels of pro-inflammatory cytokines in the arthritic joint. Conclusion: We identified acid sphingomyelinase as a novel druggable target in rheumatoid arthritis. Functional inhibitors of acid sphingomyelinase have been clinically used for decades, are well tolerated and suitable for long-term treatment. They would be immediately available for clinical development as a novel rheumatoid arthritis therapy.
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Nemeth, T., K. Futosi, J. Ruland, and A. Mocsai. "AB0098 THE EFFECT OF MALT1-DEFICIENCY ON THE EFFECTOR PHASE OF EXPERIMENTAL AUTOIMMUNE ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1348.1–1349. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1439.
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Background:The paracaspase Malt1 is a cysteine protease, which forms a complex leading to the activation of the in proinflammatory transcription factor NF-κB in lymphocytes with CARMA1 and Bcl10. Previously, we showed that the myeloid equivalent of CARMA1, Card9 is important in neutrophils in Fcγ receptor-mediated cytokine release together with Bcl10 and Malt1. In line with these findings, we observed a significant decrease in the severity of autoantibody-triggered arthritis in the absence of Card9 and Bcl10.Objectives:Our aim was to directly investigate whether the genetic deficiency of Malt1, the third component of the complex altered the process of the K/BxN serum transfer arthritis (that resembles to the effector phase of rheumatoid arthritis).Methods:We used wild type and Malt1–/–mice for our experiments. Autoantibody-mediated arthritis was induced by a single intraperitoneal injection of K/BxN serum. Clinical signs of joint inflammation were scored on a scale based on the cardinal inflammatory clues for two weeks. Ankle thickness was measured by a spring-loaded caliper.Results:Similar to the deficiency of the other two components of the complex, Malt1–/–mice showed a partial, but significant decrease in the macroscopic joint inflammation compared to arthritic serum-treated wild type animals during the entire experimental process. In line with this phenomenon, Malt1–/–animals had reduced autoantibody-triggered ankle thickening.Conclusion:Our results show that Malt1 seems to be an important molecule in the development and progression of experimental autoantibody-induced arthritis in mice, highlighting the role of the molecule as a potential therapeutic target in the future.Disclosure of Interests:None declared
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Waterborg, Claire Elisabeth Joyce, Paqui González Través, Anna Zagórska, Greg Lemke, Silke Beermann, and Fons Adrianus van de Loo. "The TAM receptors Axl and Mer play a joint-specific protective role in experimental arthritis." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 117.7. http://dx.doi.org/10.4049/jimmunol.196.supp.117.7.
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Abstract Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by an unrestrained inflammatory response in synovial joints. One family of tyrosine kinase receptors involved in anti-inflammatory feedback mechanism are Tyro3, Axl and Mer (TAM). The plasma level of the TAM receptor ligand Gas6 is significantly reduced in RA patients suggesting this feedback mechanism is impaired in RA. We investigated the individual role of each TAM receptor in experimental arthritis. Methods The KRN serum transfer model of arthritis was induced by two intraperitoneal injections of arthritic K/BxN serum in TAM receptor single gene knock-out mice (Tyro3−/−, Axl−/−, Mer−/−) and wild-type (WT) mice. Ankle joints were macroscopically scored for 7 days and knee and ankle joints were taken at the end of the experiment for histology and immunohistochemistry. Results Mer−/− mice had an increased macroscopic ankle score until day 4 whereas Axl−/− mice had an enhanced macroscopic score from day 4 until the end of the experiment. Histology of the ankle joints showed significantly increased arthritis pathology in Axl−/− mice compared to WT. In contrast, enhanced macroscopic score and arthritis pathology in the knee joints of Mer−/− mice was observed. Both in ankle and knee joints, no protective or aggravating role of Tyro3 was seen. To explain the discrepancy of Axl involvement between ankle and knee, we looked for Axl expression in synovium of naïve mice. The lining layer of ankle synovium was completely Axl-positive whereas only mild expression in the knee joints was observed. Conclusion These findings identify the TAM receptors Axl and Mer as important protective players in arthritis in addition to being expressed in a joint-specific manner.
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Thuy, Trinh Thi, Tran Duc Quan, Nguyen Thanh Tam, Nguyen Thi Hoang Anh, Nguyen Thi Cuc, Nguyen Thi Nga, Tran Van Sung, et al. "INVESTIGATING THE ANTI-INFLAMMATORY ACTIVITY OF AN ETHANOLIC EXTRACT FROM ARTOCARPUS TONKINENSIS LEAVES USING A COLLAGEN ANTIBODY-INDUCED ARTHRITIC MOUSE MODEL." Vietnam Journal of Science and Technology 56, no. 3 (June 11, 2018): 286. http://dx.doi.org/10.15625/2525-2518/56/3/11105.
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The obtained results here demonstrate that the 70% ethanolic leaf extract of A. tonkinensis (AT2), traditionally used in Vietnamese folk medicine for treating arthritic symtoms, has beneficial effects on pro-inflammatory cytokine inhibition and in an experimental arthritic mouse model. LPS-stimulated RAW 264.7 macrophages treated with AT2 showed a significant decrease in the production of IL-6 and TNFa at concentrations of 12.5, 25 and 50 µg/mL (P<0.05), indicating its potential anti-inflammatory properties. Treatment of CAIA mice with AT2 also led to diminish the incidence of arthritis at doses of 200 and 300 mg/kg body weight.
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Paras, Tyler M., Frank Percival, and Eileen McQuade. "The gut microbiome influences arthritis development in IIJ mice." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 118.16. http://dx.doi.org/10.4049/jimmunol.196.supp.118.16.
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Abstract Inherited Inflamed Joint (IIJ) mice spontaneously develop inflammatory arthritis at an early age. The gut microbiome has been implicated in several murine models for inflammatory arthritis, however the role of the microbiome in IIJ arthritis is unknown. The purpose of this study was to determine whether the gut microbiome affects arthritis development in IIJ mice and characterize the microbiome of IIJ mice in various age and disease states using next generation sequencing techniques. Pre-arthritic (pAR) IIJ mice were treated with water containing neomycin, ampicillin, vancomycin, and metronidazole for 5 weeks. Disease onset and severity was scored based on swelling of the large joints throughout the treatment period. Antibiotic treatment delayed disease onset and reduced disease severity in IIJ mice. Additionally, the IIJ gut microbiome in pAR, 5 week old arthritic mice (AR), and age matched controls (pN and NAR, respectively) were characterized using MiSeq sequencing of 16S rRNA amplicons. pAR mice were enriched with an unclassified member of the Clostridiales, whereas pN mice were dominated with species from the S24-7 family and Bacteroides, both members of the Bacteroidetes. Differences between the bacterial communities of experimental groups were apparent from the non-metric multidimensional scaling (NMDS) plots, but were not significant by PERMANOVA. Together these results suggest that the gut microflora of IIJ mice increase host susceptibility to inflammatory arthritis, which may be mediated by a unclassified member of the Clostridiales. Classical triggers of the innate immune system are also being investigated for effects on arthritis incidence and severity.
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Živná, Helena, Ljiljana Maric, Iveta Gradošová, Klára Švejkovská, Soňa Hubená, and Pavel Živný. "The Effect of Mud-Bath Therapy on Bone Status in Rats During Adjuvant Subchronic Arthritis." Acta Medica (Hradec Kralove, Czech Republic) 55, no. 3 (2012): 133–37. http://dx.doi.org/10.14712/18059694.2015.51.
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Introduction: We studied influence of mud-bath on bone status in male Wistar rats with subchronic arthritis. Methods: Arthritis was induced by 2 subplantar injections of Freund’s adjuvans with heat-killed Streptoccocus pyogenes into paw. Groups: intact (int) on chippings; (con) arthritis on chippings; (san38) arthritis on hot sand; (mu38) arthritis on hot mud; (mu21) arthritis on mild mud. Bone mineral density (BMD, g/cm2) was measured by dual energy X-ray absorptiometry and femurs were tested biomechanically. Bone markers osteocalcin (OC), PINP and CTX were analysed in bone. Results: BMD of right femur decreased vs. left in san38 (p = 0.030) and mu38 (p = 0.047). Fracture load of right/left femur (N) decreased in experimental groups, significantly in san38 (p = 0.05). Fracture threshold of neck decreased in right vs. left in experimental groups, but significantly in san38 (p = 0.05). OC decreased in mu38 vs. con (1.84 ± 0.14/2.62 ± 0.23). PINP decreased in int vs. san38 (p = 0.005) and mu21 (p < 0.001). CTX decreased in int vs. mu38 (p = 0.006) and mu21 (p = 0.005). Conclusion: The hot bath appears indifferent in relation to osteoporosis, while cold mud-bath shows good effect on bone metabolism. The cold mud-baths help to reduce arthritic inflammation and pain and thereby lead to higher mobility with positive consequence on bone.
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Kit, Yu Ya. "Proteolytic activity of IgGs from blood serum of wistar rats at experimental rheumatoid arthritis." Ukrainian Biochemical Journal 86, no. 5 (October 27, 2014): 95–101. http://dx.doi.org/10.15407/ubj86.05.095.
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Sykora, Tomas, Pavel Babal, Kristina Mikus-Kuracinova, Frantisek Drafi, Silvester Ponist, Monika Dvorakova, Pavol Janega, and Katarina Bauerova. "Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis." International Journal of Molecular Sciences 22, no. 16 (August 12, 2021): 8662. http://dx.doi.org/10.3390/ijms22168662.
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Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)—an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO—control, AIA—untreated adjuvant-induced arthritis, AIA-BIL—adjuvant-induced arthritis administrated UCB, CO-BIL—control with administrated UCB. UCB was administered intraperitoneally 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of Mycobacterium butyricum in incomplete Freund’s adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic.
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Mehdi, Quratulain. "Efficacy of Telmisartan in Pristane Induced Arthritis Rat Model." Proceedings of Shaikh Zayed Medical Complex Lahore 35, no. 3 (June 26, 2021): 6–11. http://dx.doi.org/10.47489/pszmc-801-35-3-6-11.
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Introduction: Rheumatoid arthritis is one of the most common systemic inflammatory diseases characterized by progressive damage to the joints. There is rising evidence that Renin Angiotensin Aldosterone System signaling is also involved in the inflammatory response in rheumatoid arthritis and its blockers possess anti-arthritic properties. Telmisartan is an angiotensin receptor blocker and PPAR-? agonist and its anti-arthritic effects were evaluated. Aims & Objectives: This experimental study was designed to evaluate the anti-arthritic efficacy of telmisartan in pristane induced rat model of arthritis in adult female rats. Place and duration of study: The study was conducted in the Department of Pharmacology, Army Medical College, Rawalpindi, in collaboration with National Institute of Health and Armed Forces Institute of Pathology from July 2020 to August 2020. Material & Methods: Twenty four (24) adult non-pregnant female Sprague Dawley rats were divided in three groups (n=8) designated as Group A (normal control), Group B (arthritic control) and Group C (telmisartan group) & maintained on standard diet and water adlibitum. Rheumatoid arthritis was induced in each rat of Groups B &C by a single intradermal injection of 0.5ml pristane at the base of its tail on day 0 and the disease developed in two weeks. All 3 groups were given distilled water 2.5 ml/kg from 2-4 weeks and Group C was additionally given dissolved telmisartan orally at 2 mg/kg/day. Anti-arthritic efficacy was determined by assessing arthrogram score and total leukocyte count on day 0, 14 and 28 along with histological examination done at the end of the study. Data analysis was done using SPSS version 25. Results: Healthy rats in group A maintained a unremarkable arthogram & histogram score & TLC count of 6675±350/?l during the entire study period. Telmisartan administration in Group C for two weeks after pristane induction resulted in significant reduction in arthrogram score (AS) 9.5±3.66, total leukocyte count (TLC) 7350±550/?l and histological score (HS) to 6.88±1.24 as compared to (AS) 14.50±2.07, WBC 10150±350/?L & (HS) 10.75±2.05 in Group B, left untreated with pristane alone. The intergroup comparison showed significant p value < 0.05 respectively. Conclusion: Anti-arthritic effect was shown by telmisartan as it was able to ameliorate the changes induced by pristane.
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Khan, Mahmood Ahmad, Rafat Sultana Ahmed, Nilesh Chandra, Vinod Kumar Arora, and Athar Ali. "In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis." Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 18, no. 1 (February 6, 2019): 55–70. http://dx.doi.org/10.2174/1871523017666181116092934.
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Background: Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti‐inflammatory, and immunomodulatory properties. </P><P> Objective: The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats. </P><P> Methods: To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, IL-1β, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats. </P><P> Results: Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-α, IL-1β, IL-6, transcription factor NF-κB and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-κB activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal. </P><P> Conclusion: From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.
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Ghiasian, Seyed A., Amir H. Maghsood, Asadollah Abniki, and Abbas Mirshafiey. "The Immunomodulatory Effect of Trichophyton Rubrum Exoantigens in the Treatment of Experimental Septic Arthritis." Open Microbiology Journal 11, no. 1 (May 30, 2017): 72–82. http://dx.doi.org/10.2174/1874285801711010072.
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Background:Understanding the nature and function of fungal exoantigens might lead to novel approaches in the treatment and prophylaxis of some infectious diseases. Septic arthritis represents a serious problem for medicine due to the high incidence rate and severe complications.Objective:The present study aimed at assessing the immunomodulatory effects ofTrichophyton rubrumculture filtrate as a novel compound in experimental septic arthritis.Method:The septic arthritis was haematogenously induced in Sprague-Dawley rats by a single intravenous injection of 109colony forming units of the human clinical isolateStaphylococcus aureusproducing toxic shock syndrome toxin-1.Trichophyton rubrumculture filtrate at two different doses 20 and 40 mg/kg was administered intraperituneally two days after bacterial inoculation in the treatment groups and concurrently with the appearance of clinical signs in the patient groups. The administration ofTrichophyton rubrumsolution was continued every other day for 10 injections.Results:The clinical evaluation showed thatTrichophyton rubrum-treated rats were significantly protected from disease development compared with untreated controls. This finding was correlated with results of radiological evaluation of the involved joints. Although, the inflammatory cell infiltration, cartilage/bone destruction and synovial hypertrophy had been decreased in the treatment groups in comparison with arthritic controls however, the histological changes were not significant in these two groups.Conclusion:It is possible thatTrichophyton rubrumantigens may play a role in modulating the immune responses and would be efficient in septic arthritis treatment.
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Conforti, A., S. Lussignoli, S. Bertani, R. Ortolani, G. Verlato, and P. Bellavite. "Intraperitoneal Administration of Adjuvant Inhibits the Development of Adjuvant Arthritis in Rats." International Journal of Immunopathology and Pharmacology 8, no. 2 (May 1995): 113–21. http://dx.doi.org/10.1177/039463209500800206.
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In recent years, considerable efforts have been made to develop effective therapy for autoimmune diseases by specific suppression of the autoreactive immune process without affecting the remainder of the immune system. In our study we evaluated the protective effects and therapeutic potential of Mycobacterium butyricum (Mb), the causative antigen inducing adjuvant arthritis (AA), an experimental model of autoimmune disease in the rat. The antigen was administered to rats by a different route and at concentrations 10 and 100 times lower than the inducing one. Arthritis was induced by injection of 0.6 mg of Mb in paraffin oil into the hindpaw, and the severity of disease was assessed by measurement of contralateral paw swelling every three days and primary and secondary lesions were scored on an arbitrary scale after 14, 21, and 28 days. Animals were assigned to different groups and treated intraperitoneally with different doses and schedules of Mb. The administration of 60 μg of Mb every two days, starting 6 days before arthritogenic injection until the second day after, led to a significant inhibition of the arthritic process (p< 0.001 of the arthritic index). Treatment of animals with 60 μg of Mb every two days, from day 2 to day 21 after arthritis induction caused almost total suppression of lesions. However, in both treatment schedules, animals showed important signs of peritoneal inflammation. The administration of single injection of 60 or 6 μg of Mb 10 days after arthritis induction led to an inhibition of arthritic index reaching the maximum percentage on day 14 (26% and 24% with 60 and 6 μg respectively) and was able to delay the development of oedema foot volume, without signs of local inflammation. These results confirm the ability to modulate the autoimmune process even when the immunological response is far advanced, suggesting new strategies in the therapy of human autoimmune diseases.
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Huang, Mao-Hsiung, Rei-Cheng Yang, Hueisch-Jy Ding, and Chee-Yin Chai. "Ultrasound effect on level of stress proteins and arthritic histology in experimental arthritis." Archives of Physical Medicine and Rehabilitation 80, no. 5 (May 1999): 551–56. http://dx.doi.org/10.1016/s0003-9993(99)90198-3.
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Sidhu, Maninder, and David S. Bradley. "T cell receptor V beta usage in HLA-DQ6αβ8αβ mice displaying spontaneous polyarthritis (137.31)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 137.31. http://dx.doi.org/10.4049/jimmunol.182.supp.137.31.
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Abstract Spontaneous polyarthritis (SP), an autoimmune disease that develops spontaneously in HLA-DQ6 αβ8aαβ transgenic (tg) mice, is characterized by lymphocyte infiltration in joints leading to chronic polyarthritis in the extremities similar to human rheumatoid arthritis. We examine here the CD4 T cell receptor (TCR) expression in the DQ6/8 tg mice during SP. CD4 T cells were isolated from the lymph nodes of arthritic and non-arthritic DQ6/8 tg mice at various time points, phenotyped via flow cytometry with V beta usage characterized in the CD4+CD25+ T cell population. Preferential usage of V β8.2 was increased from 9% in 2 month naïve mice to 15% in 4 month old and 20% by 8mo old arthritic mice. V β17 expressing T cells also increased from 0.02% in 2 month naïve mice to 2.8% in 4 month old arthritic mice. This is consistent with other studies that have indicated an association of Vβ8.2 TCR in the Experimental Autoimmune Encephalomyelitis and collagen-induced arthritis models. These results support our hypothesis that activated CD4 T cells expressing Vβ8.2 TCR are the predominantly pathogenic; autoreactive T cells involved in SP. Selective depletion of these T cells using anti-Vβ8.2 antibodies will confirm their involvement. Application of such strategies of immune intervention can be helpful in humans to control or reduce the disease progression in the stages of disease initiation. The study was supported by NIH-NIAMS AR45657
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Yassin, Fatma El-Zahraa S., Rokaia Ahmed, Doha Mohamed, Hanem Abdel-Tawab, Khaled Aziz El-Din, and Alshaimaa A. Alghriany. "Histopathological Appraisal of the Synergistic Effect of Ginger and Curcuma on an Arthritic Rat Model." Current Topics in Nutraceutical Research 20, no. 2 (September 13, 2021): 407–15. http://dx.doi.org/10.37290/ctnr2641-452x.20:407-415.
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Collagen-induced arthritis is the most used experimental model for rheumatoid arthritis. Using this model, we have appraised the histopathological effects of ginger and curcuma alone and their combination. Arthritis was induced by immunization with an emulsion of Freund’s adjuvant mixed with alum-precipitated collagen. Half of the animals from each group were sacrificed on the 21st day of arthritis induction and the remaining on the 26th day. Body-weight gain and erythrocyte sedimentation rate showed marked improvement in the treated groups (P < 0.001). A spectrum of intra-articular histopathological changes was assessed in groups II to V. The untreated arthritic rats in group II exhibited inflammation and vascularity in the synovium compared to the control rats in group I. The treated rats in groups III (ginger alone), IV (curcuma alone), and V (ginger and curcuma) showed an improvement of the hyperplastic synovium. These findings show that the combined use of ginger and curcuma may be a good option for the treatment of collagen-induced arthritis. This makes a case for a human clinical trial of the use of ginger and curcuma for arthritis.
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Rosillo, M. A., M. Sánchez-Hidalgo, and C. Alarcón-de-la-Lastra. "Extra-virgin olive oil and its phenolic extract prevent inflammatory response and joint damage in murine experimental arthritis." Grasas y Aceites 67, no. 4 (December 1, 2016): 158. http://dx.doi.org/10.3989/gya.0449161.
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The consumption of EVOO in Mediterranean countries has shown beneficial effects. A wide range of evidence indicates that the phenolic compounds present in EVOO are endowed with anti-inflammatory properties. In this work, we evaluated the effects of dietary EVOO and treatment with its phenolic extract (PE) in a model of RA, the collagen-induced arthritis (CIA) in mice. On day 0, DBA-1/J mice were immunized with bovine collagen type II (CII). On day 21, the mice received a booster injection. We have demonstrated that EVOO and its PE decreases joint edema, cell migration, cartilage degradation and bone erosion. Our data indicate that dietary EVOO and PE treatment inhibit JNK, p38 and signal transducer and STAT-3. In addition, both EVOO and PE decrease NF-κB translocation leading to the down-regulation of the arthritic process. These results support the interest of natural diet components in the development of therapeutic products for arthritic conditions.
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Karydis, Anastasios, Indra Sandal, Jiwen Luo, Amanda Prislovsky, Amanda Gamboa, Edward F. Rosloniec, and David D. Brand. "Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers." PLOS ONE 16, no. 4 (April 15, 2021): e0250177. http://dx.doi.org/10.1371/journal.pone.0250177.
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Our previous studies have shown that inoculation of the oral cavity of “humanized” B6.DR1/4 mice with the periodontal pathogen Porphyromonas gingivalis results in an increase in the percentage of circulating Th17 cells, loss of bone and an exacerbation of experimental autoimmune arthritis. The aim of this study was to assess the role played by the human HLA-DRβ molecule containing the shared epitope supplied as a transgene to I-A˚ (murine class II null) C57BL/6 (B6) mice in driving these findings. We compared various immune response parameters as well as alveolar and peri-articular bone loss between humanized B6.DR1 (or B6.DR4) mice and their WT (B6) counterparts. We found that the presence of the shared epitope in the context of inoculation with P. gingivalis enhanced the percentage of Th17 cells generated, dramatically enhanced bone loss and importantly allowed for the generation of CCP2⁺ ACPAs that are not found in C57BL/6 or DBA/1 arthritic mouse serum. Due to the exceedingly complex nature of environmental factors impacting on genetic elements, it has been difficult to unravel mechanisms that drive autoimmune arthritis in susceptible individuals. The findings in this study may provide one small piece of this puzzle that can help us to better understand part of this complexity.
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Anderton, S. M., R. van der Zee, B. Prakken, A. Noordzij, and W. van Eden. "Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis." Journal of Experimental Medicine 181, no. 3 (March 1, 1995): 943–52. http://dx.doi.org/10.1084/jem.181.3.943.
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Lewis rats are susceptible to several forms of experimental arthritis-induced using heat-killed Mycobacterium tuberculosis (adjuvant arthritis, or AA), streptococcal cell walls, collagen type II, and the lipoidal amine CP20961. Prior immunization with the mycobacterial 65-kD heat shock protein (hsp65) was reported to protect against AA, and other athritis models not using M. tuberculosis, via a T cell-mediated mechanism. Hsp65 shares 48% amino acid identity with mammalian hsp60, which is expressed at elevated levels in inflamed synovia. Several studies have reported cross-reactive T cell recognition of mycobacterial hsp65 and self hsp60 in arthritic and normal individuals. We previously described nine major histocompatibility complex class II-restricted epitopes in mycobacterial hsp65 recognized by Lewis rat T cells. Of these only one, covering the 256-270 sequence, primed for cross-reactive T cell responses to the corresponding region of rat hsp60. Here we have tested each hsp65 epitope for protective activity by immunizing rats with synthetic peptides. A peptide containing the 256-270 epitope, which induced cross-reactive T cells, was the only one able to confer protection against AA. Similarly, administration of a T cell line specific for this epitope protected against AA. Preimmunization with the 256-270 epitope induced T cells that responded to heat-shocked syngeneic antigen-presenting cells, and also protected against CP20961-induced arthritis, indicating that activation of T cells, recognizing an epitope in self hsp60 can protect against arthritis induced without mycobacteria. Therefore, in contrast to the accepted concept that cross-reactive T cell recognition of foreign and self antigens might induce aggressive autoimmune disease, we propose that cross-reactivity between bacterial and self hsp60 might also be used to maintain a protective self-reactive T cell population. This discovery might have important implications for understanding T cell-mediated regulation of inflammation.
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Wolski, A., E. Palombo-Kinne, F. Wolf, F. Emmrich, W. Becker, and R. W. Kinne. "Minimal contribution of cell-bound antibodies to the immunoscintigraphy of inflamed joints with 99mTc-anti-CD4 monoclonal antibodies." Nuklearmedizin 41, no. 03 (2002): 129–34. http://dx.doi.org/10.1055/s-0038-1623888.
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Summary Aim: The cellular joint infiltrate in rheumatoid arthritis patients is rich in CD4-positive T-helper lymphocytes and macrophages, rendering anti-CD4 monoclonal antibodies (mAbs) suitable for specific immunoscintigraphy of human/ experimental arthritis. Following intravenous injection, however, mAbs are present both in the free form and bound to CD4-positive, circulating monocytes and T-cells. Thus, the present study aimed at analyzing the relative contribution of the free and the cell-bound component to the imaging of inflamed joints in experimental adjuvant arthritis (AA). Methods: AA rat peritoneal macrophages or lymph node T-cells were incubated in vitro with saturating amounts of 99mTc-anti-CD4 mAb (W3/25) and injected i.v. into rats with AA. Results: In vitro release of 99mTc-anti-CD4 mAb from the cells was limited (on average 1.57%/h for macrophages and 0.84%/h for T-cells). Following i.v. injection, whole body/joint scans and tissue measurements showed only negligible accumulation of radioactivity in inflamed ankle joints (tissue: 0.22 and 0.34% of the injected activity, respectively), whereas the radioactivity was concentrated in liver (tissue: 79% and 71%, respectively), kidney, and urinary bladder. Unlike macrophages, however, anti-CD4 mAb-coated T-cells significantly accumulated in lymphoid organs, the inflamed synovial membrane of the ankle joints, as well as in elbow and knee joints. Conclusion: While the overall contribution of cell-bound mAbs to the imaging of arthritic joints with anti-CD4 mAbs is minimal, differential accumulation of macrophages and T-cells in lymphoid organs and the inflamed synovial membrane indicates preferential migration patterns of these 2 cell populations in arthritic rats. Although only validated for 99mTc-anti-CD4 mAbs, extrapolation of the results to other anticellular mAbs with similar affinity for their antigen may be possible.
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Flick, Matthew J., Christine M. La Jeunesse, Kathryn E. Talmage, David P. Witte, Joseph Palumbo, Malinda D. Pinkerton, Sherry Thornton, and Jay L. Degen. "Fibrin(ogen) Exacerbates Inflammatory Joint Disease Via a Mechanism Linked to Its αMβ2 Binading Motif." Blood 108, no. 11 (November 16, 2006): 64. http://dx.doi.org/10.1182/blood.v108.11.64.64.
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Abstract Activation of the hemostatic system is a common pathological feature of severe inflammatory processes. In the context of inflammatory joint disease, articular fibrin deposition is a prominent feature that has been hypothesized to contribute to the derangements in immune/inflammatory processes and tissue reorganization that lead to debilitating and irreversible damage within arthritic joints. We directly examined the role of fibrin(ogen) in the progression of inflammatory joint disease using the well-established experimental setting of collagen-induced arthritis (CIA). Mice with genetically-imposed fibrinogen deficiency (Fib−/−) were found to exhibit significantly reduced macroscopic arthritic disease incidence, progression, and severity in the paws relative to littermate controls throughout the evaluation period. Consistent with the macroscopic observations, qualitative and quantitative histological analysis of distal- and knee-joint sections revealed a significant decrease in all joint disease parameters (e.g., inflammatory cell infiltrates, synovial hyperplasia, edema, and cartilage/bone loss) in Fib−/− mice as compared to fibrinogen-sufficient controls. Fibrin(ogen) has been shown to promote pro-inflammatory activity through engagement of the leukocyte integrin receptor αMβ2 (Mac-1). To determine if fibrinogen/αMβ2 interactions promote the pathogenesis of arthritis, we compared CIA progression in mice expressing fibrinogen that lacks the leukocyte integrin receptor αMβ2 binding motif (i.e., Fibγ390–396A mice). We observed decreased gross and histological inflammatory joint disease in Fibγ390–396A mice relative to control animals. This diminution in arthritic disease severity was comparable to that observed in Fib−/− mice despite the maintenance of normal clotting function in Fibγ390–396A animals. In comparison, CIA studies in mice expressing a mutant form of fibrinogen lacking the platelet integrin receptor αIIbβ3 binding motif showed that this feature of fibrinogen was not an essential driver of arthritis. The reduction in macroscopic and histological arthritic disease observed in CIA-challenged Fibγ390–396A mice was accompanied by reduced local mRNA levels of the pro-inflammatory cytokines TNF α, IL-6, and IL-1β in paws relative to paws from control animals. This data suggests that fibrin(ogen) may function upstream of local production of these critical inflammatory mediators. Consistent with this hypothesis, fibrinogen deficiency did not diminish arthritic disease driven by TNFα-overexpression. Together, these data support the view that local fibrin deposition is an important determinant of inflammatory joint disease and that one mechanism by which fibrin promotes arthritic disease is through leukocyte activation events downstream of αMβ2 engagement.
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Lin, S., X. Gu, F. Wang, and W. Tan. "POS0002 PI16 REPRESSES FOXP3 EXPRESSION IN T REGULATORY CELLS AND EXACERBATES AUTOIMMUNE ARTHRITIS VIA INHIBITING THE K48-LINKED POLYUBIQUITIN DEGRADATION OF BMI-1." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 203.2–203. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2756.
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Background:Regulatory T cells (Tregs) play an essential role in maintaining self-tolerance and immune homeostasis. Abnormalities in the quantity or function of Treg cells are believed in RA patients, contributing to the inability to suppress autoimmunity and proinflammatory cytokines. Forkhead box P3 (Foxp3) is a crucial transcription factor for the development and differentiation of Tregs. How Tregs lose Foxp3 expression under inflammatory milieu remains largely unknown. Peptidase inhibitor 16 (PI16) is a member of the CAP (Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1) protein family and its function are largely poor understood. In a genome-wide expression profiling study for identifying human Foxp3 target genes revealed PI16 was expressed on the cell surface of >80% of resting human CD25+ Foxp3+ Tregs. In the inflamed joint of juvenile idiopathic arthritis revealed a low number of PI16+ Tregs but high number of Th17 cells. However, little is known the function role of PI16 on Tregs or on RA development.Objectives:To investigate the role of peptidase inhibitor 16 (PI16) on the key T regulatory (Tregs) cells transcription factor Foxp3 expression and on the development of autoimmune arthritis.Methods:The expression of PI16 in blood, synovial fluid, inflamed joints were examined in Rheumatoid arthritis (RA) patients and in arthritic mice. Arthritis symptom, histological features and Foxp3 expression in PI16 transgenic (PI16Tg) arthritic mice were examined. Posttranslational mechanisms on PI16-mediated Foxp3 expression were analyzed. The specific role PI16 on Foxp3 expression was validated in conditional knockout (KO) mice.Results:The expression of PI16 was significantly increased in PBMC, serum, synovial tissue from RA patients or arthritic mice compared with controls. PI16Tg arthritic mice exhibited obvious inflammation, synovial hyperplasia and articular cartilage destruction in the joints compared with those in wild-type mice (WT) arthritic mice.Foxp3 is downregulated in splenic T cells and synovial tissue from PI16Tg arthritic mice. Naïve T cells derived from PI16Tg arthritic mice showed the decreased capacity to differentiate into Tregs. Polycomb-group (PcG) proteins complex molecule of Bmi-1 was significant increase in Tregs and joint tissue from PI16Tg arthritic mice. A direct interaction between 1-95AA domains of PI16 and 169 and 436 domains of Bmi-1 in Tregs promoter was observed. The binding of PI16 with Bmi-1 in the Foxp3 promoter inhibit the K48-linked polyubiquitin degradation of Bmi-1 at lysine site 72 and 153 region, which prompts the repressive histone modification of H3K27me3 and H2AK119ub, and inhibits the active histone modification of H3K4me3. Furthermore, conditional knockout of PI16 in Tregs retarded Foxp3 loss and blunted disease progression in experimental arthritis.Conclusion:PI16 represses Foxp3 expression by mediating histone modification via inhibiting K48-linked polyubiquitin degradation of Bmi-1 in Foxp3 promoter, contributing to disease progression in arthritic mice.Disclosure of Interests:None declared.
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Ramos-Romero, Sara, Francisco J. Pérez-Cano, Teresa Pérez-Berezo, Cristina Castellote, Angels Franch, and Margarida Castell. "Effect of a cocoa flavonoid-enriched diet on experimental autoimmune arthritis." British Journal of Nutrition 107, no. 4 (July 19, 2011): 523–32. http://dx.doi.org/10.1017/s000711451100328x.
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Previously we established that a cocoa-enriched diet in young rats reduces specific antibody production and the T helper (Th) lymphocyte proportion in lymphoid tissues. The aim of the present study was to ascertain the modulatory ability of a cocoa flavonoid-enriched diet on collagen-induced arthritis (CIA), which is mediated by anti-collagen autoantibody response and Th lymphocyte activation. Female Louvain (LOU) rats were fed with a cocoa-enriched diet, beginning 2 weeks before CIA induction. Hind-paw swelling and serum cytokine and anti-collagen antibody concentrations were determined. Anti-collagen antibody-secreting cell counts and lymphocyte subset proportions were established in inguinal lymph nodes (ILN). Reactive oxygen species (ROS), nitric oxide (NO) and TNFα produced by peritoneal macrophages were determined. Although arthritic cocoa-fed rats showed a similar hind-paw swelling time course as the arthritic animals fed a standard diet, the cocoa intake was able to decrease specific IgG2a, IgG2b and IgG2c titres. Moreover, cocoa intake in CIA rats reduced ROS production, TNFα and NO release from peritoneal macrophages, and decreased the Th:cytotoxic T cell ratio in ILN. In conclusion, a cocoa flavonoid-enriched diet in LOU rats with CIA produced no effect on hind-paw swelling but was able to modulate the specific antibody response and also the Th lymphocyte proportion, as well as the synthesis of pro-inflammatory mediators from peritoneal macrophages. Therefore, a cocoa-enriched diet could be a good adjuvant therapy in disorders with oxidative stress or autoimmune pathogenesis.