Journal articles on the topic 'Immunoregulatory properties and inflammation'
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1
Nie, Hong. "Novel immunoregulatory properties of EGCG on reducing inflammation in EAE." Frontiers in Bioscience 18, no. 1 (2013): 332. http://dx.doi.org/10.2741/4104.
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Petrovsky, F. I., Yu A. Petrovskaya, L. M. Ogorodova, and V. Yu Serebrov. "Cytokines and nitric oxide in case of bronchial asthma." Bulletin of Siberian Medicine 1, no. 1 (March 30, 2002): 70–74. http://dx.doi.org/10.20538/1682-0363-2002-1-70-74.
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Complex interactions between nitric oxide and cytokines of atopic inflammation are presented. The effects of interleukin-4 on nitric oxide synthesis, immunoregulatory properties of nitric oxide and its influence on Th1/Th2 balance are described.
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Semenkov, N. N., V. S. Gorin, S. G. Zhabin, L. V. Renge, and N. G. Potekhin. "Inhibitors of proteolysis and plasminogen of blood serum in parturient women with an uncomplicated course of the postpartum period." Kazan medical journal 79, no. 2 (March 25, 1998): 135–36. http://dx.doi.org/10.17816/kazmj63776.
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Recent studies have shown that proteolysis inhibitors can be regarded as markers of inflammation with immunoregulatory properties. From this point of view, the study of inhibitors of proteinases in blood serum of puerperas with an uncomplicated course of the postpartum period is of great scientific and practical interest.
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Shi, Chenchen, Haipeng Li, Yifu Yang, and Lifei Hou. "Anti-Inflammatory and Immunoregulatory Functions of Artemisinin and Its Derivatives." Mediators of Inflammation 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/435713.
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Artemisinin and its derivatives are widely used in the world as the first-line antimalarial drug. Recently, growing evidences reveal that artemisinin and its derivatives also possess potent anti-inflammatory and immunoregulatory properties. Meanwhile, researchers around the world are still exploring the unknown bioactivities of artemisinin derivatives. In this review, we provide a comprehensive discussion on recent advances of artemisinin derivatives affecting inflammation and autoimmunity, the underlying molecular mechanisms, and also drug development of artemisinins beyond antimalarial functions.
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Harrell, Carl Randall, Vladislav Volarevic, Valentin Djonov, and Ana Volarevic. "Therapeutic Potential of Exosomes Derived from Adipose Tissue-Sourced Mesenchymal Stem Cells in the Treatment of Neural and Retinal Diseases." International Journal of Molecular Sciences 23, no. 9 (April 19, 2022): 4487. http://dx.doi.org/10.3390/ijms23094487.
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Therapeutic agents that are able to prevent or attenuate inflammation and ischemia-induced injury of neural and retinal cells could be used for the treatment of neural and retinal diseases. Exosomes derived from adipose tissue-sourced mesenchymal stem cells (AT-MSC-Exos) are extracellular vesicles that contain neurotrophins, immunoregulatory and angio-modulatory factors secreted by their parental cells. AT-MSC-Exos are enriched with bioactive molecules (microRNAs (miRNAs), enzymes, cytokines, chemokines, immunoregulatory, trophic, and growth factors), that alleviate inflammation and promote the survival of injured cells in neural and retinal tissues. Due to the nano-sized dimension and bilayer lipid envelope, AT-MSC-Exos easily bypass blood–brain and blood–retinal barriers and deliver their cargo directly into the target cells. Accordingly, a large number of experimental studies demonstrated the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases. By delivering neurotrophins, AT-MSC-Exos prevent apoptosis of injured neurons and retinal cells and promote neuritogenesis. AT-MSC-Exos alleviate inflammation in the injured brain, spinal cord, and retinas by delivering immunoregulatory factors in immune cells, suppressing their inflammatory properties. AT-MSC-Exos may act as biological mediators that deliver pro-angiogenic miRNAs in endothelial cells, enabling re-vascularization of ischemic neural and retinal tissues. Herewith, we summarized current knowledge about molecular mechanisms which were responsible for the beneficial effects of AT-MSC-Exos in the treatment of neural and retinal diseases, emphasizing their therapeutic potential in neurology and ophthalmology.
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Dasgupta, Suryasarathi, Deniz Erturk-Hasdemir, and Dennis Kasper. "Characterization of a DC Presenting a Microbial Polysaccharide to Regulatory T cells. (49.9)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 49.9. http://dx.doi.org/10.4049/jimmunol.188.supp.49.9.
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Abstract Bacteroides fragilis Polysaccharide A (PSA) is a unique commensal microflora molecule which has shown potent CD4+T cell mediated IL-10 dependent anti-inflammatory properties in various murine models. Little is known about how these immunoregulatory T cells are induced in order to control inflammation. We first observed that PSA dependent augmentation of regulatory T cells correlated with frequency of B220+CD11cint cells in MLN. We focused majorly on Plasmacytoid dendritic cells (PDCs), which have been implicated as tolerogenic DCs in other inflammatory situations. We observed higher expression of TLR2, a previously reported PSA receptor, in PSA treated PDCs compared to media control in vitro. Isolated PDCs from wild type compared to TLR2 deficient PDCs significantly augmented the liberation of IL-10 from CD4T cells in presence of PSA (p=0.0046), a process mediated by co-stimulators ICOSL and CD86. In a TNBS induced colonic inflammation model to study PSA mediated protection, the frequency of PDCs correlated significantly but inversely with cumulative colitis score (R2=0.4377, p=0.0002) suggesting an immunoregulatory role of these cells. Interestingly, neither protection nor change in PDCs was observed in TLR2-/-mice. In addition, PSA failed to protect mice when either PDCs were depleted or co-stimulators inhibited in vivo with monoclonal antibodies. This work suggests a tolerogenic or immunoregulatory role for PDCs most probably by generating regulatory features in T cells.
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Nair, Meera G., Yurong Du, Jacqueline G. Perrigoue, Colby Zaph, Justin J. Taylor, Michael Goldschmidt, Gary P. Swain, et al. "Alternatively activated macrophage-derived RELM-α is a negative regulator of type 2 inflammation in the lung." Journal of Experimental Medicine 206, no. 4 (April 6, 2009): 937–52. http://dx.doi.org/10.1084/jem.20082048.
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Differentiation and recruitment of alternatively activated macrophages (AAMacs) are hallmarks of several inflammatory conditions associated with infection, allergy, diabetes, and cancer. AAMacs are defined by the expression of Arginase 1, chitinase-like molecules, and resistin-like molecule (RELM) α/FIZZ1; however, the influence of these molecules on the development, progression, or resolution of inflammatory diseases is unknown. We describe the generation of RELM-α–deficient (Retnla−/−) mice and use a model of T helper type 2 (Th2) cytokine-dependent lung inflammation to identify an immunoregulatory role for RELM-α. After challenge with Schistosoma mansoni (Sm) eggs, Retnla−/− mice developed exacerbated lung inflammation compared with their wild-type counterparts, characterized by excessive pulmonary vascularization, increased size of egg-induced granulomas, and elevated fibrosis. Associated with increased disease severity, Sm egg–challenged Retnla−/− mice exhibited elevated expression of pathogen-specific CD4+ T cell–derived Th2 cytokines. Consistent with immunoregulatory properties, recombinant RELM-α could bind to macrophages and effector CD4+ Th2 cells and inhibited Th2 cytokine production in a Bruton's tyrosine kinase–dependent manner. Additionally, Retnla−/− AAMacs promoted exaggerated antigen-specific Th2 cell differentiation. Collectively, these data identify a previously unrecognized role for AAMac-derived RELM-α in limiting the pathogenesis of Th2 cytokine-mediated pulmonary inflammation, in part through the regulation of CD4+ T cell responses.
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Wongchitrat, Prapimpun, Mayuri Shukla, Ramaswamy Sharma, Piyarat Govitrapong, and Russel J. Reiter. "Role of Melatonin on Virus-Induced Neuropathogenesis—A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection." Antioxidants 10, no. 1 (January 2, 2021): 47. http://dx.doi.org/10.3390/antiox10010047.
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Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and encephalitis are common. Recently, extensive research-based studies have revealed and acknowledged the clinical and preventive roles of melatonin in some viral diseases. Melatonin has been shown to have antiviral properties against several viral infections which are accompanied by neurological symptoms. The beneficial properties of melatonin relate to its properties as a potent antioxidant, anti-inflammatory, and immunoregulatory molecule and its neuroprotective effects. In this review, what is known about the therapeutic role of melatonin in virus-induced neuropathogenesis is summarized and discussed.
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Tilg, Herbert, and Arthur Kaser. "Interferons and Their Role in Inflammation." Current Pharmaceutical Design 5, no. 10 (October 1999): 771–85. http://dx.doi.org/10.2174/1381612805666230111210939.
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Cytokines are pleiotropic molecules showing a wide variety of biologic functions on various cells and tissues, and several different cytokines exert similar and overlapping functions on certain cells. Interferons (IFNs), among the first cytokines identified, play a crucial role in human disease. The IFN cytokine family consists of type I IFNs (IFN-a and IFN- ) and type II IFN (IFN-y). In the first decades of IFN research, type I IFNs were considered primarily as viral inhibitors, whereas type II IFN, also termed "immune IFN", was generally considered to be uniquely involved in immune reactions. This view has changed considerably in the last years. The importance of type I IFNs in inflammation, immunoregulation and T-cell responses has been identified and has changed dramatically our interpretation of the biological relevance of type I and II IFNs. Recent data suggest that IFN-a is a multifunctional immunomodulatory cytokine with profound effects on the cytokine cascade including several anti-inflammatory properties, whereas IFN-y remains a classical proinflammatory cytokine. These different effects on critical mediators of inflammation may also explain why type I and II IFNs are clinically successful in different diseases. These newly identified immunoregulatory and anti-inflammatory functions of type I IFNs may be of importance in the treatment of diseases such as chronic viral hepatitis or multiple sclerosis and help to explain some of the mechanisms of IFNs.
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Morianos, Ioannis, and Maria Semitekolou. "Dendritic Cells: Critical Regulators of Allergic Asthma." International Journal of Molecular Sciences 21, no. 21 (October 26, 2020): 7930. http://dx.doi.org/10.3390/ijms21217930.
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Allergic asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness (AHR), chronic airway inflammation, and excessive T helper (Th) type 2 immune responses against harmless airborne allergens. Dendritic cells (DCs) represent the most potent antigen-presenting cells of the immune system that act as a bridge between innate and adaptive immunity. Pertinent to allergic asthma, distinct DC subsets are known to play a central role in initiating and maintaining allergen driven Th2 immune responses in the airways. Nevertheless, seminal studies have demonstrated that DCs can also restrain excessive asthmatic responses and thus contribute to the resolution of allergic airway inflammation and the maintenance of pulmonary tolerance. Notably, the transfer of tolerogenic DCs in vivo suppresses Th2 allergic responses and protects or even reverses established allergic airway inflammation. Thus, the identification of novel DC subsets that possess immunoregulatory properties and can efficiently control aberrant asthmatic responses is critical for the re-establishment of tolerance and the amelioration of the asthmatic disease phenotype.
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Exley, Mark A., Laura Hand, Donal O'Shea, and Lydia Lynch. "Interplay between the immune system and adipose tissue in obesity." Journal of Endocrinology 223, no. 2 (September 16, 2014): R41—R48. http://dx.doi.org/10.1530/joe-13-0516.
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Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. Alongside its major role in energy storage, WAT is an important endocrine organ, producing many bioactive molecules, termed adipokines, which not only serve as regulators of systemic metabolism, but also possess immunoregulatory properties. Furthermore, WAT contains a unique immune cell repertoire, including an accumulation of leukocytes that are rare in other locations. These include alternatively activated macrophages, invariant natural killer T cells, and regulatory T cells. Disruption of resident adipose leukocyte homeostasis contributes to obesity-associated inflammation and consequent metabolic disorder. Despite many recent advances in this new field of immuno-metabolism, fundamental questions of why and how inflammation arises as obesity develops are not yet fully understood. Exploring the distinct immune system of adipose tissue is fundamental to our understanding of the endocrine as well as immune systems. In this review, we discuss the roles of adipose tissue leukocytes in the transition to obesity and progression of inflammation and highlight potential anti-inflammatory therapies for combating obesity-related pathology.
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Zhong, Yajie, Xuan Zhang, and Waipo Chong. "Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases." International Journal of Molecular Sciences 23, no. 2 (January 6, 2022): 627. http://dx.doi.org/10.3390/ijms23020627.
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Interleukin (IL)-24 belongs to the IL-10 family and signals through two receptor complexes, i.e., IL-20RA/IL-20RB and IL-20RB/IL22RA1. It is a multifunctional cytokine that can regulate immune response, tissue homeostasis, host defense, and oncogenesis. Elevation of IL-24 is associated with chronic inflammation and autoimmune diseases, such as psoriasis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Its pathogenicity has been confirmed by inducing inflammation and immune cell infiltration for tissue damage. However, recent studies also revealed their suppressive functions in regulating immune cells, including T cells, B cells, natural killer (NK) cells, and macrophages. The tolerogenic properties of IL-24 were reported in various animal models of autoimmune diseases, suggesting the complex functions of IL-24 in regulating autoimmunity. In this review, we discuss the immunoregulatory functions of IL-24 and its roles in autoimmune diseases.
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Zhou, Juan, Haneen Noori, Ian Burkovskiy, J. Lafreniere, Melanie Kelly, and Christian Lehmann. "Modulation of the Endocannabinoid System Following Central Nervous System Injury." International Journal of Molecular Sciences 20, no. 2 (January 17, 2019): 388. http://dx.doi.org/10.3390/ijms20020388.
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Central nervous system (CNS) injury, such as stroke or trauma, is known to increase susceptibility to various infections that adversely affect patient outcomes (CNS injury-induced immunodepression—CIDS). The endocannabinoid system (ECS) has been shown to have immunoregulatory properties. Therefore, the ECS might represent a druggable target to overcome CIDS. Evidence suggests that cannabinoid type 2 receptor (CB2R) activation can be protective during the early pro-inflammatory phase after CNS injury, as it limits neuro-inflammation and, therefore, attenuates CIDS severity. In the later phase post CNS injury, CB2R inhibition is suggested as a promising pharmacologic strategy to restore immune function in order to prevent infection.
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Pavlov, O. V., S. V. Chepanov, A. V. Selutin, and S. A. Selkov. "Platelet-leukocyte interactions: immunoregulatory role and pathophysiological relevance." Medical Immunology (Russia) 24, no. 5 (October 31, 2022): 871–88. http://dx.doi.org/10.15789/1563-0625-pli-2511.
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Blood platelets are the central players in thrombosis and blood coagulation. Moreover, they also exhibit immunoregulatory properties and bridge hemostasis and immunity. Morphological and functional characteristics of the platelets ensure continuous surveillance for the vascular system, recognition of different hazards, development of appropriate response and recruitment of immune cells. Indirect platelet-leukocyte interactions are mediated by immunoregulatory molecules that are released, along with coagulation and thrombosis factors in the course of platelet activation and degranulation. Chemokines, cytokines, growth factors, some of which are synthesized de novo, are released from activated platelets and modulate cellular functions, thus modulating both innate and adaptive immune response. Activated platelets enter contacts with immune cells to form heterotypic aggregates, i.e., platelet-leukocyte complexes that reside in blood circulation along with other blood cells. The aggregate formation and stabilization is mediated by interaction between the molecules expressed on the surface of platelets and leukocytes, in particular, P-selectin (CD62P) and PSGL-1 (CD162). Platelet-monocyte and platelet-neutrophil complexes are most abundant, with platelet-monocyte aggregates being most stable. Moreover, the platelet-derived microvesicles also interact with leukocytes to form heterotypic aggregates, thus, probably, modulating the immune cell functions via transfer of non-coding RNA molecules. Formation of platelet-leukocyte complexes results into mutual activation of platelets and leukocytes. Platelets and platelet-derived microvesicles stimulate phagocytic activity, cytokine secretion, and generation of reactive oxygen species in monocytes and neutrophils, inducing formation of neutrophilic extracellular traps and procoagulant phenotype in monocytes. The blood platelets regulate monocyte differentiation, promote adhesion, as well as transmigration of lymphocytes and NK cells. At the sites of inflammation, platelets enhance extravasation and infiltration of leukocytes into the damaged tissue. Impaired interactions of platelets with endothelial layer and immune cells may underlie pathogenic conditions. Increased level of circulating plateletleukocyte complexes is observed in various disorders including cardiovascular diseases, acute ischemic stroke, respiratory disorders, renal pathologies, liver diseases, diabetes, reproductive disorders, bacterial and viral infections. Further studies of platelet-leukocyte interactions are warranted to unveil pathogenic mechanisms and to develop new therapeutic approaches.
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Effendi, Wiwin Is, Tatsuya Nagano, Helmia Hasan, and Resti Yudhawati. "Immunoregulatory Property of C-Type Lectin-Like Receptors in Fibrosing Interstitial Lung Diseases." International Journal of Molecular Sciences 21, no. 10 (May 22, 2020): 3665. http://dx.doi.org/10.3390/ijms21103665.
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The innate immune system identifies exogenous threats or endogenous stress through germline-encoded receptors called pattern recognition receptors (PRRs) that initiate consecutive downstream signaling pathways to control immune responses. However, the contribution of the immune system and inflammation to fibrosing interstitial lung diseases (ILD) remains poorly understood. Immunoreceptor tyrosine-based motif-bearing C-type lectin-like receptors (CTLRs) may interact with various immune cells during tissue injury and wound repair processes. Dectin-1 is a CTLR with dominant mechanisms manifested through its intracellular signaling cascades, which regulate fibrosis-promoting properties through gene transcription and cytokine activation. Additionally, immune impairment in ILD facilitates microbiome colonization; hence, Dectin-1 is the master protector in host pulmonary defense against fungal invasion. Recent progress in determining the signaling pathways that control the balance of fibrosis has implicated immunoreceptor tyrosine-based motif-bearing CTLRs as being involved, either directly or indirectly, in the pathogenesis of fibrosing ILD.
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McDonnell, Cormac, Erin Soule, Patrick Walsh, James O'Donnell, and Roger Preston. "The Immunoregulatory Activities of Activated Protein C in Inflammatory Disease." Seminars in Thrombosis and Hemostasis 44, no. 02 (December 12, 2017): 167–75. http://dx.doi.org/10.1055/s-0037-1608910.
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AbstractTissue injury prompts the initiation of host defense responses to limit blood loss, restrict pathogen entry, and promote repair. Biochemical and cellular pathways that lead to blood coagulation serve a fundamental role in generating a physical barrier at the wound site, but have also evolved to promote immune response to injury. Similarly, anticoagulant pathways that attenuate clot formation also regulate innate and adaptive immune responses. Of particular importance is activated protein C (APC) which serves as a principal regulator of thrombin generation, shapes the innate immune response to infection, and has been shown to contribute to the adaptive immune response in several preclinical models of autoimmune disease. APC controls blood coagulation by proteolytic degradation of procoagulant activated cofactors essential for fibrin clot development, but also cleaves multiple additional substrates and interacts with cell surface receptors to exert additional physiologically important roles. In this review, we focus on the molecular mechanisms utilized by APC to limit inflammation and, in particular, current understanding of the basis for APC anticoagulant and signaling activities. In particular, we provide an overview of established and emerging signaling pathways initiated by APC on endothelial cells, monocytes, neutrophils, dendritic cells, and T cells to control and regulate immune cell physiology. Finally, we consider the impact of APC activity in the context of both acute and chronic inflammatory disease, and the continuing efforts to harness the immunoregulatory properties of recombinant APC for therapeutic use.
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Zhang, Hong-liang, Jiang Wu, and Jie Zhu. "The Role of Apolipoprotein E in Guillain-Barré Syndrome and Experimental Autoimmune Neuritis." Journal of Biomedicine and Biotechnology 2010 (2010): 1–12. http://dx.doi.org/10.1155/2010/357412.
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Apolipoprotein E (apoE) is a 34.2 kDa glycosylated protein characterized by its wide tissue distribution and multiple functions. ApoE has been widely studied in lipid metabolism, cardiocerebrovascular diseases, and neurodegenerative diseases like Alzheimer's disease and mild cognitive impairment, and so forth. Recently, a growing body of evidence has pointed to nonlipid related properties of apoE, including suppression of T cell proliferation, regulation of macrophage function, facilitation of lipid antigen presentation by CD1 molecules to natural killer T (NKT) cells, and modulation of inflammation and oxidation. By these properties, apoE impacts physiology and pathophysiology at multiple levels. The present paper summarizes updated studies on the immunoregulatory function of apoE, with special focus on isoform-specific effects of apoE on Guillain-Barré syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN).
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Dembele, Marieme, Gabriel N. Kaufman, Di Xue, Marianne Beland, and Bruce D. Mazer. "DCIR is an Important Regulatory Molecule in Allergic Inflammation." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 191.19. http://dx.doi.org/10.4049/jimmunol.196.supp.191.19.
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Abstract The dendritic cell immunoreceptor (DCIR) is an inhibitory C-type lection receptor possessing immunoregulatory properties. We have shown that DCIR serves as a receptor for IVIg. In this study, we sought to determine its requirement in modulating IVIg mechanism of action by using a murine model of allergic of airways disease. Wild type (WT) and DCIR−/− mice were sensitized and challenged with ovalbumin (OVA), and lung histopathology, bronchoalveolar lavage and phenotyping of inflammatory cells were performed. We further studied the effect of IVIg on allergen uptake and processing of CD11c+ cells in vitro. Briefly, bone marrow-derived dendritic cells from WT, DCIR−/− and Fcr2b−/− mice were treated with IVIg prior to exposure to OVA-ALEXA-647 or DQ-OVA. DCIR−/− mice exhibit exacerbated pulmonary inflammation and eosinophilia compared to WT mice; this phenotype is rescued by IVIg treatment as in WT mice. Furthermore, IVIg significantly impairs the antigen uptake and processing machinery of dendritic cells from WT and DCIR−/− derived BMDCs but not that of Fcr2b−/−-derived BMDCs. In conclusion, DCIR is important in regulating allergic airway inflammation and its presence is not essential for IVIg to function. DCIR appears to be required for normal regulation of pulmonary inflammation.
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Wang, Mengyuan, Quan Yuan, and Liang Xie. "Mesenchymal Stem Cell-Based Immunomodulation: Properties and Clinical Application." Stem Cells International 2018 (June 14, 2018): 1–12. http://dx.doi.org/10.1155/2018/3057624.
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Mesenchymal stem cells (MSCs) are multipotent stem cells characterized by self-renewal, production of clonal cell populations, and multilineage differentiation. They exist in nearly all tissues and play a significant role in tissue repair and regeneration. Additionally, MSCs possess wide immunoregulatory properties via interaction with immune cells in both innate and adaptive immune systems, leading to immunosuppression of various effector functions. Numerous bioactive molecules secreted by MSCs, particularly cytokines, growth factors, and chemokines, exert autocrine/paracrine effects that modulate the physiological processes of MSCs. These invaluable virtues of MSCs provide new insight into potential treatments for tissue damage and inflammation. In particular, their extensive immunosuppressive properties are being explored for promising therapeutic application in immune disorders. Recently, clinical trials for MSC-mediated therapies have rapidly developed for immune-related diseases following reports from preclinical studies declaring their therapeutic safety and efficacy. Though immunotherapy of MSCs remains controversial, these clinical trials pave the way for their widespread therapeutic application in immune-based diseases. In this review, we will summarize and update the latest research findings and clinical trials on MSC-based immunomodulation.
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Hsieh, Chia-Chen, Wen-Huang Peng, Hsien-Hao Tseng, Shan-Yuan Liang, Li-Jen Chen, and Jen-Chieh Tsai. "The Protective Role of Garlic on Allergen-Induced Airway Inflammation in Mice." American Journal of Chinese Medicine 47, no. 05 (January 2019): 1099–112. http://dx.doi.org/10.1142/s0192415x19500563.
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Asthma is the most prevalent chronic respiratory disease worldwide. Garlic extracts have long been used as a food source and in traditional medicine. Crude extracts of garlic are used as an anti-inflammatory agent and have been reported to exhibit antiasthmatic properties. However, molecular mechanisms of garlic extracts in the context of antiasthmatic airway inflammation are still unclear. In this study, the antiasthmatic effect of garlic extracts on Th1, Th2, and Th3 cytokine profiles and immunoregulatory mechanism were explored using an animal model of allergic asthma. Garlic extracts significantly reduced total inflammatory cell counts and eosinophil infiltration and decreased the production of Dermatophagoides pteronyssinus IgE in serum and Th1/Th2/Th3 cytokine in bronchoalveolar fluid. Enzyme-linked immunosorbent assay analysis demonstrated that garlic extracts downregulated the levels of cytokines and chemokines, namely Th2-related IL-4, IL-5, and IL-13; but they simultaneously upregulated Th1-related IFN-[Formula: see text], IL-12, and Th3-related IL-10 and TGF-[Formula: see text] expression in BALF. The mechanism may be ascribed to the modulation of Th1-, Th2-, and Th3-related cytokine imbalance.
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Du, Tao, and Ying-Jian Zhu. "The Regulation of Inflammatory Mediators in Acute Kidney Injury via Exogenous Mesenchymal Stem Cells." Mediators of Inflammation 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/261697.
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Acute kidney injury (AKI) remains to be an independent risk factor for mortality and morbidity. Inflammation is believed to play a major role in the pathophysiology of AKI. Exogenous mesenchymal stem cells (MSCs) are now under extensive investigation as a potential therapy for AKI. Various preclinical studies indicated the beneficial effects of MSCs in alleviating renal injury and accelerating tissue repair. However the mechanisms responsible for these effects are incompletely understood. In the recent years, anti-inflammatory/immunoregulatory properties of MSCs have become one of the important issues in the treatment of AKI. This review will summarize the current literature on the regulation of inflammatory mediators via exogenous MSCs contributing to the recovery from AKI.
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Chytilová, Mária, Radomíra Nemcová, Soňa Gancarčíková, Dagmar Mudroňová, and Ľudmila Tkáčiková. "Flax-seed oil and Lactobacillus plantarum supplementation modulate TLR and NF-κB gene expression in enterotoxigenic Escherichia coli challenged gnotobiotic pigs." Acta Veterinaria Hungarica 62, no. 4 (December 1, 2014): 463–72. http://dx.doi.org/10.1556/avet.2014.024.
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The present study analyses the effect of flax-seed oil rich in n-3 polyunsaturated fatty acids (PUFAs), the probiotic strain Lactobacillus plantarum — Biocenol™ LP96 and their combination on the expression level of selected Toll-like receptor (TLR) genes (TLR2, TLR4, TLR5, TLR9) and their downstream molecules (myeloid differentiation factor 88, MyD88; nuclear factor-κB, NF-κB) in the jejunum of gnotobiotic pigs challenged with enterotoxigenic Escherichia coli (ETEC). The results show that both immunomodulators are able to modulate the RNA level of at least one of the target molecules and thus regulate pathogeninduced inflammation. We confirmed that not only probiotic lactobacilli or flaxseed oil alone but also their synergistic action has great potential in the prevention and treatment of porcine colibacillosis. The results give an insight into one of the possible mechanisms by which natural agents, such as probiotic lactobacilli and flax-seed oil, exert their immunoregulatory properties during pathogen-induced inflammation.
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Coste, Chloé, Nathalie Gérard, Chau Phi Dinh, Antoine Bruguière, Caroline Rouger, Sow Tein Leong, Khalijah Awang, Pascal Richomme, Séverine Derbré, and Béatrice Charreau. "Targeting MHC Regulation Using Polycyclic Polyprenylated Acylphloroglucinols Isolated from Garcinia bancana." Biomolecules 10, no. 9 (September 2, 2020): 1266. http://dx.doi.org/10.3390/biom10091266.
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Modulation of major histocompatibility complex (MHC) expression using drugs has been proposed to control immunity. Phytochemical investigations on Garcinia species have allowed the isolation of bioactive compounds such as polycyclic polyprenylated acylphloroglucinols (PPAPs). PPAPs such as guttiferone J (1), display anti-inflammatory and immunoregulatory activities while garcinol (4) is a histone acetyltransferases (HAT) p300 inhibitor. This study reports on the isolation, identification and biological characterization of two other PPAPs, i.e., xanthochymol (2) and guttiferone F (3) from Garcinia bancana, sharing structural analogy with guttiferone J (1) and garcinol (4). We show that PPAPs 1–4 efficiently downregulated the expression of several MHC molecules (HLA-class I, -class II, MICA/B and HLA-E) at the surface of human primary endothelial cells upon inflammation. Mechanistically, PPAPs 1–4 reduce MHC proteins by decreasing the expression and phosphorylation of the transcription factor STAT1 involved in MHC upregulation mediated by IFN-γ. Loss of STAT1 activity results from inhibition of HAT CBP/p300 activity reflected by a hypoacetylation state. The binding interactions to p300 were confirmed through molecular docking. Loss of STAT1 impairs the expression of CIITA and GATA2 but also TAP1 and Tapasin required for peptide loading and transport of MHC. Overall, we identified new PPAPs issued from Garcinia bancana with potential immunoregulatory properties.
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Furuzawa-Carballeda, Janette, Perla Macip-Rodríguez, Angeles S. Galindo-Feria, David Cruz-Robles, Virgina Soto-Abraham, Sergio Escobar-Hernández, Diana Aguilar, Deshiré Alpizar-Rodríguez, Karen Férez-Blando, and Luis Llorente. "Polymerized-Type I Collagen Induces Upregulation of Foxp3-Expressing CD4 Regulatory T Cells and Downregulation of IL-17-Producing CD4+T Cells (Th17) Cells in Collagen-Induced Arthritis." Clinical and Developmental Immunology 2012 (2012): 1–11. http://dx.doi.org/10.1155/2012/618608.
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Previous studies showed that polymerized-type I collagen (polymerized collagen) exhibits potent immunoregulatory properties. This work evaluated the effect of intramuscular administration of polymerized collagen in early and established collagen-induced arthritis (CIA) in mice and analyzed changes in Th subsets following therapy. Incidence of CIA was of 100% in mice challenged with type II collagen. Clinimorphometric analysis showed a downregulation of inflammation after administration of all treatments (P<0.05). Histological analysis showed that the CIA-mice group had extensive bone erosion, pannus and severe focal inflammatory infiltrates. In contrast, there was a remarkable reduction in the severity of arthritis in mice under polymerized collagen, methotrexate or methotrexate/polymerized collagen treatment. Polymerized Collagen but not methotrexate induced tissue joint regeneration. Polymerized Collagen and methotrexate/polymerized collagen but not methotrexate alone induces downregulation of CD4+/IL17A+T cells and upregulation of Tregs and CD4+/IFN-γ+T cells. Thus, Polymerized Collagen could be an effective therapeutic agent in early and established rheumatoid arthritis by exerting downregulation of autoimmune inflammation.
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Labonte, Adam, Sun-Sang Sung, and Young Hahn. "Scavenger receptor CD204+ macrophages play an immunoregulatory role in hepatic viral infection (VIR1P.971)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 74.13. http://dx.doi.org/10.4049/jimmunol.192.supp.74.13.
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Abstract Macrophages (MΦ) are important for the activation and direction of innate and adaptive immune responses, however their role in liver infection is particularly poorly understood, in part due to the presence of functionally distinct subsets within the population. The MΦ scavenger receptor CD204/SRA is a marker for alternatively activated (M2) MΦ, which have anti-inflammatory properties and participate in wound healing and tissue remodeling. To understand the function of CD204+ MΦ on regulating liver inflammation, we examined the activation and differentiation of MΦ in a murine model of hepatic viral infection. Our studies revealed that CD204 was upregulated on circulating and liver-resident MΦ following tail vein injection of adenovirus or MCMV. CD204+ macrophages appear to express high levels of PD-L1 and IL-10, suggesting an alteration of MΦ phenotype. Interestingly, virally infected CD204-deficient mice had less liver CD8+ T cells than their wild type counterparts and these T cells produced less IFNγ and granzyme B. In contrast, liver NK and NKT cell populations in knockout and WT mice were similar in size, but NK cells from CD204 deficient mice displayed increased granzyme B staining following infection. These data indicate that CD204+ MΦ play a critical role in modulating the immune response to hepatic viral infection.
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Wang, Mengyuan, Jiang Xie, Cong Wang, Dingping Zhong, Liang Xie, and Hongzhi Fang. "Immunomodulatory Properties of Stem Cells in Periodontitis: Current Status and Future Prospective." Stem Cells International 2020 (July 8, 2020): 1–14. http://dx.doi.org/10.1155/2020/9836518.
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Periodontitis is the sixth-most prevalent chronic inflammatory disease and gradually devastates tooth-supporting tissue. The complexity of periodontal tissue and the local inflammatory microenvironment poses great challenges to tissue repair. Recently, stem cells have been considered a promising strategy to treat tissue damage and inflammation because of their remarkable properties, including stemness, proliferation, migration, multilineage differentiation, and immunomodulation. Several varieties of stem cells can potentially be applied to periodontal regeneration, including dental mesenchymal stem cells (DMSCs), nonodontogenic stem cells, and induced pluripotent stem cells (iPSCs). In particular, these stem cells possess extensive immunoregulatory capacities. In periodontitis, these cells can exert anti-inflammatory effects and regenerate the periodontium. Stem cells derived from infected tissue possess typical stem cell characteristics with lower immunogenicity and immunosuppression. Several studies have demonstrated that these cells can also regenerate the periodontium. Furthermore, the interaction of stem cells with the surrounding infected microenvironment is critical to periodontal tissue repair. Though the immunomodulatory capabilities of stem cells are not entirely clarified, they show promise for therapeutic application in periodontitis. Here, we summarize the potential of stem cells for periodontium regeneration in periodontitis and focus on their characteristics and immunomodulatory properties as well as challenges and perspectives.
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Kawanishi, Kunio. "Diverse properties of the mesothelial cells in health and disease." Pleura and Peritoneum 1, no. 2 (June 1, 2016): 79–89. http://dx.doi.org/10.1515/pp-2016-0009.
Full textAbstract:
AbstractMesothelial cells (MCs) form the superficial anatomic layer of serosal membranes, including pleura, pericardium, peritoneum, and the tunica of the reproductive organs. MCs produce a protective, non-adhesive barrier against physical and biochemical damages. MCs express a wide range of phenotypic markers, including vimentin and cytokeratins. MCs play key roles in fluid transport and inflammation, as reflected by the modulation of biochemical markers such as transporters, adhesion molecules, cytokines, growth factors, reactive oxygen species and their scavengers. MCs synthesize extracellular matrix related molecules, and the surface of MC microvilli secretes a highly hydrophilic protective barrier, “glycocalyx”, consisting mainly of glycosaminoglycans. MCs maintain a balance between procoagulant and fibrinolytic activation by producing a whole range of regulators, can synthetize fibrin and therefore form adhesions. Synthesis and recognition of hyaluronan and sialic acids might be a new insight to explain immunoactive and immunoregulatory properties of MCs. Epithelial to mesenchymal transition of MCs may involve serosal repair and remodeling. MCs might also play a role in the development and remodeling of visceral adipose tissue. Taken together, MCs play important roles in health and disease in serosal cavities of the body. The mesothelium is not just a membrane and should be considered as an organ.
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Rua, Rejane, Jane Lee, Alex Silva, Maric Dragan, Kory Johnson, and Dorian B. McGavern. "Meningeal inflammation drives long-term engraftment by monocytes that impair CNS immunity." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 168.4. http://dx.doi.org/10.4049/jimmunol.200.supp.168.4.
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Abstract Tissue-resident macrophages have an embryonic origin and can be replenished by blood monocytes in some tissues during adulthood. Under steady-state conditions, infiltrating monocytes can share phenotypic and genotypic features with their embryonically-derived counterparts. However, little is known about the properties of monocytes/macrophages that establish tissue residency after an inflammatory challenge. The meninges of the central nervous system (CNS) are populated by a dense network of specialized macrophages that serve as immune sentinels. Following infection by lymphocytic choriomeningitis virus (LCMV), these resident macrophages become activated by innate inflammatory cytokines, acquire viral antigens, and are targeted by infiltrating cytotoxic T lymphocytes (CTL), which leads to their depletion. Innate cytokines and chemokines released by CTL also promote a massive recruitment of inflammatory monocytes from the periphery. Surprisingly, these infiltrating monocytes engraft the meningeal niche and remain in situ several months after viral clearance. This leads to significant phenotypic and functional changes in meningeal immunity – a defect that can be partially restored by blocking IFNγ signaling. Importantly, macrophages that establish residency in the meninges after an inflammatory event are deficient in bacterial and immunoregulatory sensors, which impedes their ability to detect pathogens and dampen subsequent meningeal immune responses. Collectively, these data indicate that monocytes can engraft the meninges after an inflammatory challenge and contribute to long-term alterations in CNS immunity.
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Tynecka, Marlena, Marcin Moniuszko, and Andrzej Eljaszewicz. "Old Friends with Unexploited Perspectives: Current Advances in Mesenchymal Stem Cell-Based Therapies in Asthma." Stem Cell Reviews and Reports 17, no. 4 (March 1, 2021): 1323–42. http://dx.doi.org/10.1007/s12015-021-10137-7.
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AbstractMesenchymal stem cells (MSCs) have a great regenerative and immunomodulatory potential that was successfully tested in numerous pre-clinical and clinical studies of various degenerative, hematological and inflammatory disorders. Over the last few decades, substantial immunoregulatory effects of MSC treatment were widely observed in different experimental models of asthma. Therefore, it is tempting to speculate that stem cell-based treatment could become an attractive means to better suppress asthmatic airway inflammation, especially in subjects resistant to currently available anti-inflammatory therapies. In this review, we discuss mechanisms accounting for potent immunosuppressive properties of MSCs and the rationale for their use in asthma. We describe in detail an intriguing interplay between MSCs and other crucial players in the immune system as well as lung microenvironment. Finally, we reveal the potential of MSCs in maintaining airway epithelial integrity and alleviating lung remodeling. Graphical abstract
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Olkowska-Truchanowicz, Joanna, Agata Białoszewska, Aneta Zwierzchowska, Alicja Sztokfisz-Ignasiak, Izabela Janiuk, Filip Dąbrowski, Grażyna Korczak-Kowalska, Ewa Barcz, Katarzyna Bocian, and Jacek Malejczyk. "Peritoneal Fluid from Patients with Ovarian Endometriosis Displays Immunosuppressive Potential and Stimulates Th2 Response." International Journal of Molecular Sciences 22, no. 15 (July 29, 2021): 8134. http://dx.doi.org/10.3390/ijms22158134.
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Endometriosis is a common gynaecological disorder characterized by the ectopic growth of endometrial tissue outside the uterine cavity. It is associated with chronic pelvic inflammation and autoimmune reactivity manifesting by autoantibody production and abrogated cellular immune responses. Endometriotic peritoneal fluid contains various infiltrating leucocyte populations and a bulk of proinflammatory and immunoregulatory cytokines. However, the nature and significance of the peritoneal milieu in women with endometriosis still remains obscure. Therefore, the aim of the present study was to investigate the immunoregulatory activity of the peritoneal fluid (PF) from women with endometriosis. The peritoneal fluid samples were collected during laparoscopic surgery from 30 women with and without endometriosis. Immunoregulatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) and chemokines (CCL2, CCL5, CXCL8 and CXCL9) were evaluated in PF and culture supernatants generated by unstimulated and CD3/CD28/IL-2-stimulated CD4+ T cells cultured in the presence of PF. The effect of PF on the generation of Treg and Th17 cells in CD4+ T cell cultures, as well as the natural cytotoxic activity of peripheral blood mononuclear cells, was also investigated. Concentrations of IL-6, IL-10, CCL2, CXCL8 and CXCL9 were significantly upregulated in the PF from women with endometriosis when compared to control women, whereas concentrations of other cytokines and chemokines were unaffected. The culturing of unstimulated and CD3/CD28/IL-2-stimulated CD4+ T cells in the presence of endometriotic PF resulted in the downregulation of their IL-2, IFN-γ, IL-17A and TNF production as compared to culture medium alone. On the other side, endometriotic PF significantly stimulated the production of IL-4 and IL-10. Endometriotic PF also stimulated the release of CCL2 and CXCL8, whereas the production of CCL5 and CXCL9 was downregulated. Endometriotic PF stimulated the generation of Treg cells and had an inhibitory effect on the generation of Th17 cells in cultures of CD4+ T cells. It also inhibited the NK cell cytotoxic activity of the peripheral blood lymphocytes. These results strongly imply that the PF from patients with endometriosis has immunoregulatory/immunosuppressive activity and shifts the Th1/Th2 cytokine balance toward the Th2 response, which may account for deviation of local and systemic immune responses. However, a similar trend, albeit not a statistically significant one, was also observed in case of PF from women without endometriosis, thus suggesting that peritoneal milieu may in general display some immunoregulatory/immunosuppressive properties. It should be stressed, however, that our present observations were made on a relatively small number of PF samples and further studies are needed to reveal possible mechanism(s) responsible for this phenomenon.
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Holopainen, Minna, Ulla Impola, Petri Lehenkari, Saara Laitinen, and Erja Kerkelä. "Human Mesenchymal Stromal Cell Secretome Promotes the Immunoregulatory Phenotype and Phagocytosis Activity in Human Macrophages." Cells 9, no. 9 (September 22, 2020): 2142. http://dx.doi.org/10.3390/cells9092142.
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Human mesenchymal stromal/stem cells (hMSCs) show great promise in cell therapy due to their immunomodulatory properties. The overall immunomodulatory response of hMSCs resembles the resolution of inflammation, in which lipid mediators and regulatory macrophages (Mregs) play key roles. We investigated the effect of hMSC cell-cell contact and secretome on macrophages polarized and activated toward Mreg phenotype. Moreover, we studied the effect of supplemented polyunsaturated fatty acids (PUFAs): docosahexaenoic acid (DHA) and arachidonic acid, the precursors of lipid mediators, on hMSC immunomodulation. Our results show that unlike hMSC cell-cell contact, the hMSC secretome markedly increased the CD206 expression in both Mreg-polarized and Mreg-activated macrophages. Moreover, the secretome enhanced the expression of programmed death-ligand 1 on Mreg-polarized macrophages and Mer receptor tyrosine kinase on Mreg-activated macrophages. Remarkably, these changes were translated into improved Candida albicans phagocytosis activity of macrophages. Taken together, these results demonstrate that the hMSC secretome promotes the immunoregulatory and proresolving phenotype of Mregs. Intriguingly, DHA supplementation to hMSCs resulted in a more potentiated immunomodulation with increased CD163 expression and decreased gene expression of matrix metalloproteinase 2 in Mreg-polarized macrophages. These findings highlight the potential of PUFA supplementations as an easy and safe method to improve the hMSC therapeutic potential.
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Chu, Chung-Ching, Niwa Ali, Panagiotis Karagiannis, Paola Di Meglio, Ania Skowera, Luca Napolitano, Guillermo Barinaga, et al. "Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation." Journal of Experimental Medicine 209, no. 5 (April 30, 2012): 935–45. http://dx.doi.org/10.1084/jem.20112583.
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Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141+ DDCs). CD141+ DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D3 (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141+ DDCs from human blood DCs. These CD141+ DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141+ DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141+ DDC-like cells have potential clinical use for their capacity to induce immune tolerance.
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Largo, Raquel, María José Martínez-Calatrava, Olga Sánchez-Pernaute, M. Esther Marcos, Juan Moreno-Rubio, César Aparicio, Jesús Egido, and Gabriel Herrero-Beaumont. "Effect of a high dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis." American Journal of Physiology-Heart and Circulatory Physiology 297, no. 1 (July 2009): H268—H276. http://dx.doi.org/10.1152/ajpheart.00142.2009.
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Glucosamine sulfate (GS) is a glycosaminoglycan with anti-inflammatory and immunoregulatory properties. Here we set out to explore the effect of GS administration on markers of systemic and local inflammation in rabbits with atherosclerosis aggravated by chronic arthritis. Atherosclerosis was induced in rabbits by maintaining them on a hyperlipidemic diet after producing an endothelial lesion in the femoral arteries. Simultaneously, chronic arthritis was induced in these animals by repeated intra-articular injections of ovalbumin in previously immunized rabbits. A group of these rabbits was treated prophylactically with oral GS (500 mg·kg−1·day−1), and, when the animals were killed, serum was extracted and peripheral blood mononuclear cells (PBMC) were isolated. Furthermore, the femoral arteries, thoracic aorta, and synovial membranes were examined in gene expression studies and histologically. GS administration reduced circulating levels of the C-reactive protein and of interleukin-6. GS also lowered nuclear factor-κB activation in PBMC, and it downregulated the expression of both the CCL2 (monocyte chemoattractant protein) and cyclooxygenase-2 genes in these cells. Lesions at the femoral wall were milder after GS treatment, as reflected by the intimal-to-media thickened ratio and the absence of aortic lesions. Indeed, GS also attenuated the histological lesions in synovial tissue. In a combined rabbit model of chronic arthritis and atherosclerosis, orally administered GS reduced the markers of inflammation in peripheral blood, as well as the femoral and synovial membrane lesions. GS also prevented the development of inflammation-associated aortic lesions. These results suggest an atheroprotective effect of GS.
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Feola, David J., Beth A. Garvy, Theodore J. Cory, Susan E. Birket, Heather Hoy, Don Hayes, and Brian S. Murphy. "Azithromycin Alters Macrophage Phenotype and Pulmonary Compartmentalization during Lung Infection with Pseudomonas." Antimicrobial Agents and Chemotherapy 54, no. 6 (March 15, 2010): 2437–47. http://dx.doi.org/10.1128/aac.01424-09.
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ABSTRACT Infection with mucoid strains of Pseudomonas aeruginosa in chronic inflammatory diseases of the airway is difficult to eradicate and can cause excessive inflammation. The roles of alternatively activated and regulatory subsets of macrophages in this pathophysiological process are not well characterized. We previously demonstrated that azithromycin induces an alternatively activated macrophage-like phenotype in vitro. In the present study, we tested whether azithromycin affects the macrophage activation status and migration in the lungs of P. aeruginosa-infected mice. C57BL/6 mice received daily doses of oral azithromycin and were infected intratracheally with a mucoid strain of P. aeruginosa. The properties of macrophage activation, immune cell infiltration, and markers of pulmonary inflammation in the lung interstitial and alveolar compartments were evaluated postinfection. Markers of alternative macrophage activation were induced by azithromycin treatment, including the surface expression of the mannose receptor, the upregulation of arginase 1, and a decrease in the production of proinflammatory cytokines. Additionally, azithromycin increased the number of CD11b+ monocytes and CD4+ T cells that infiltrated the alveolar compartment. A predominant subset of CD11b+ cells was Gr-1 positive (Gr-1+), indicative of a subset of cells that has been shown to be immunoregulatory. These differences corresponded to decreases in neutrophil influx into the lung parenchyma and alteration of the characteristics of peribronchiolar inflammation without any change in the clearance of the organism. These results suggest that the immunomodulatory effects of azithromycin are associated with the induction of alternative and regulatory macrophage activation characteristics and alteration of cellular compartmentalization during infection.
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Sartor, RB. "Role of Intestinal Microflora in Initiation and Perpetuation of Inflammatory Bowel Disease." Canadian Journal of Gastroenterology 4, no. 7 (1990): 271–77. http://dx.doi.org/10.1155/1990/857305.
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Ulcerative colitis and Crohn's disease occur in regions of the intestine colonized by the highest concentrations of normal flora bacteria and resemble certain chronic bacterial, viral or parasitic infections. However, the role of endogenous and pathogenic bacteria in the induction and perpetuation of chronic idiopathic intestinal inflammation remains controversial. No convincing evidence incriminates a single bacterial, mycobacterial or viral agent as the cause of a high percentage of cases of idiopathic inflammatory bowel disease (IBD). Subtle alterations of luminal microbial flora are nearly impossible to detect, but concentrations of certain anaerobic bacteria, including Bacteroides vulgatus, are increased in active Crohn's disease and correlate with disease activity. Recent investigations suggest mechanisms which bacteria may induce an autoimmune response through molecular mimicry or alterations in host antigens or immunoregulation. Intestinal bacteria contain formylated peptides and cell wall polymers ( endotoxin and peptidoglycan-polysaccharide complexes) which have potent and well characterized inflammatory and immunoregulatory properties and can produce acute and chronic intestinal and systemic inflammation in experimental animals. These proinflammatory molecules are probably absorbed more readily in IBO due ro increased mucosa! permeability during active and perhaps quiescent phases of disease. While the primary mechanisms of intestinal injury remain unknown, it is likely that commensal bacteria and their products amplify and perpetuate the inflammatory response of IBO and may be responsible for extraintestinal manifestations in addition to the frequent septic complications of these diseases.
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MacDonald, Iona J., Chien-Chung Huang, Shan-Chi Liu, and Chih-Hsin Tang. "Reconsidering the Role of Melatonin in Rheumatoid Arthritis." International Journal of Molecular Sciences 21, no. 8 (April 20, 2020): 2877. http://dx.doi.org/10.3390/ijms21082877.
Full textAbstract:
Rheumatoid arthritis (RA) is an inflammatory joint disorder characterized by synovial proliferation and inflammation, with eventual joint destruction if inadequately treated. Modern therapies approved for RA target the proinflammatory cytokines or Janus kinases that mediate the initiation and progression of the disease. However, these agents fail to benefit all patients with RA, and many lose therapeutic responsiveness over time. More effective or adjuvant treatments are needed. Melatonin has shown beneficial activity in several animal models and clinical trials of inflammatory autoimmune diseases, but the role of melatonin is controversial in RA. Some research suggests that melatonin enhances proinflammatory activities and thus promotes disease activity in RA, while other work has documented substantial anti-inflammatory and immunoregulatory properties of melatonin in preclinical models of arthritis. In addition, disturbance of the circadian rhythm is associated with RA development and melatonin has been found to affect clock gene expression in joints of RA. This review summarizes current understanding about the immunopathogenic characteristics of melatonin in RA disease. Comprehensive consideration is required by clinical rheumatologists to balance the contradictory effects.
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Sarsenova, Madina, Assel Issabekova, Saule Abisheva, Kristina Rutskaya-Moroshan, Vyacheslav Ogay, and Arman Saparov. "Mesenchymal Stem Cell-Based Therapy for Rheumatoid Arthritis." International Journal of Molecular Sciences 22, no. 21 (October 27, 2021): 11592. http://dx.doi.org/10.3390/ijms222111592.
Full textAbstract:
Mesenchymal stem cells (MSCs) have great potential to differentiate into various types of cells, including but not limited to, adipocytes, chondrocytes and osteoblasts. In addition to their progenitor characteristics, MSCs hold unique immunomodulatory properties that provide new opportunities in the treatment of autoimmune diseases, and can serve as a promising tool in stem cell-based therapy. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that deteriorates quality and function of the synovium membrane, resulting in chronic inflammation, pain and progressive cartilage and bone destruction. The mechanism of RA pathogenesis is associated with dysregulation of innate and adaptive immunity. Current conventional treatments by steroid drugs, antirheumatic drugs and biological agents are being applied in clinical practice. However, long-term use of these drugs causes side effects, and some RA patients may acquire resistance to these drugs. In this regard, recently investigated MSC-based therapy is considered as a promising approach in RA treatment. In this study, we review conventional and modern treatment approaches, such as MSC-based therapy through the understanding of the link between MSCs and the innate and adaptive immune systems. Moreover, we discuss recent achievements in preclinical and clinical studies as well as various strategies for the enhancement of MSC immunoregulatory properties.
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Guidry, Tera V., Robert L. Hunter, and Jeffrey K. Actor. "CD3+ cells transfer the hypersensitive granulomatous response to mycobacterial glycolipid trehalose 6,6′-dimycolate in mice." Microbiology 152, no. 12 (December 1, 2006): 3765–75. http://dx.doi.org/10.1099/mic.0.29290-0.
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The granulomatous response is the characteristic histological feature of Mycobacterium tuberculosis infection that is essential for organism containment. Trehalose 6,6-dimycolate (TDM), a cell-wall glycolipid present on most mycobacterial species, has been implicated in the pathogenesis of M. tuberculosis infection. TDM has potent immunoregulatory and inflammatory properties, and can be used to model granulomatous reactions that mimic, in part, pathology caused during active infection. This study examined the hypersensitive granulomatous response, focusing on cellular responses specific to TDM. Lungs from mice immunized with TDM emulsion demonstrated exacerbated histological damage, inflammation, and lymphocytic infiltration upon subsequent challenge with TDM. Splenocytes recovered from these mice demonstrated significant interferon (IFN)-γ production during recall response to TDM, as well as increased production of proinflammatory mediators (tumour necrosis factor-α, interleukin-6 and macrophage inflammatory protein-1α). The exacerbated response could be adoptively transferred to naïve mice. Administration of non-adherent lymphocytes or purified CD3+ cells from TDM-immunized mice led to increased inflammation, lymphocytic infiltration, and vascular endothelial cell damage upon challenge with TDM. Recipient mice that received immunized CD3+ lymphocytes demonstrated significant increases in Th1-type cytokines and proinflammatory mediators in lung tissue following TDM challenge. When CD1d−/− mice were immunized with TDM, they failed to generate a specific IFN-γ response, suggesting a role for this molecule in the generation of hypersensitivity. These experiments provide further evidence for the involvement of TDM-specific CD3+ T cells in pathological damage elicited during M. tuberculosis infection.
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Schulze, Hendrik, Johann Hornbacher, Paulina Wasserfurth, Thomas Reichel, Thorben Günther, Ulrich Krings, Karsten Krüger, Andreas Hahn, Jutta Papenbrock, and Jan P. Schuchardt. "Immunomodulating Effect of the Consumption of Watercress (Nasturtium officinale) on Exercise-Induced Inflammation in Humans." Foods 10, no. 8 (July 30, 2021): 1774. http://dx.doi.org/10.3390/foods10081774.
Full textAbstract:
The vegetable watercress (Nasturtium officinale R.Br.) is, besides being a generally nutritious food, a rich source of glucosinolates. Gluconasturtiin, the predominant glucosinolate in watercress, has been shown to have several health beneficial properties through its bioactive breakdown product phenethyl isothiocyanate. Little is known about the immunoregulatory effects of watercress. Moreover, anti-inflammatory effects have mostly been shown in in vitro or in animal models. Hence, we conducted a proof-of-concept study to investigate the effects of watercress on the human immune system. In a cross-over intervention study, 19 healthy subjects (26.5 ± 4.3 years; 14 males, 5 females) were given a single dose (85 g) of fresh self-grown watercress or a control meal. Two hours later, a 30 min high-intensity workout was conducted to promote exercise-induced inflammation. Blood samples were drawn before, 5 min after, and 3 h after the exercise unit. Inflammatory blood markers (IL-1β, IL-6, IL-10, TNF-α, MCP-1, MMP-9) were analyzed in whole blood cultures after ex vivo immune cell stimulation via lipopolysaccharides. A mild pro-inflammatory reaction was observed after watercress consumption indicated by an increase in IL-1β, IL-6, and TNF-α, whereas the immune response was more pronounced for both pro-inflammatory and anti-inflammatory markers (IL-1β, IL-6, IL-10, TNF-α) after the exercise unit compared to the control meal. During the recovery phase, watercress consumption led to a stronger anti-inflammatory downregulation of the pro-inflammatory cytokines IL-6 and TNF-α. In conclusion, we propose that watercress causes a stronger pro-inflammatory response and anti-inflammatory counter-regulation during and after exercise. The clinical relevance of these changes should be verified in future studies.
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Kim, Sang Yong, Jiang Li, Abigail C. Burr, Hashini Batugedara, Tara Nordgren, Xingxing Zang, and Meera G. Nair. "Resistin-like molecule alpha (RELMα) dampens lung inflammation and promotes wound healing in helminth infection and a 3D lung repair model." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 185.9. http://dx.doi.org/10.4049/jimmunol.202.supp.185.9.
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Abstract RELMα is a small secreted and immunoregulatory protein, also known as hypoxia-induced mitogenic factor (HIMF) and found in inflammatory zone (FIZZ). RELMα, produced by macrophages and epithelial cells in the lung and intestine, has recently been shown by our lab and others to induce wound healing during Nippostrongylus brasiliensis (Nb) infection. However, the mechanisms by which RELMα activates wound healing pathways and what cell-types are activated by RELMα are unclear. We generated constitutive RELMα−/−/TdTomato-red (TdT) reporter mice to delete the RELMα gene and track RELMα promoter activity. We found that following Nb infection, RELMα−/− macrophages exhibited reduced expression of genes associated with wound healing such as Arg1, Mmp19 and Pdgfra. To complement the RELMα−/− mouse in vivo studies, a new endotoxin-free RELMα-human Fc fusion protein was constructed and purified. A RELMα capture assay with the fusion protein demonstrated that RELMα binds to macrophage cell line RAW 264.7. Moreover, 3D lung scaffold and wound healing assays showed that RELMα-Fc promoted tissue repair by lung epithelial cells and mesenchymal stem cells. Lastly, RELMα function in vivo was characterized by RELMα-Fc fusion protein treatment of Nb-infected RELMα−/−/TdT mice, which downregulated immune cell recruitment in the lung compared to control Fc. Ongoing studies include identification of the RELMα receptor using the RELMα fusion proteins and testing whether the wound healing properties of RELMα are effective in the intestine following Heligosomoides polygyrus infection.
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Boztok Ozgermen, Basak, Pinar Can, İrem Sancak, Eylul Akpinar, Ferda Pinarli, Ahmet Ceylan, Dogukan Ozen, and Asuman Ozen. "Transplantation of limbal derived MSCs grown on contact lenses in dogs with dry eye syndrome - can stem cells help?" Veterinarski arhiv 91, no. 4 (September 15, 2021): 349–58. http://dx.doi.org/10.24099/vet.arhiv.0951.
Full textAbstract:
Keratoconjunctivitis Sicca (KCS), also known as “dry eye syndrome”, is a common ocular disease in dogs, caused by inflammation of the lacrimal gland, resulting in decreased tear production. Efforts are being made to develop alternative therapies in order to prevent lifelong use of drugs for patients with KCS. Mesenchymal stem cells (MSCs) are known to be effective in the treatment of many immune-mediated diseases in human and animal models due to their immunoregulatory properties. The aim of this study was to transplant limbal mesenchymal stem cells (LMSCs) to the ocular surface on contact lenses and to evaluate the therapeutic effects of the LMSCs by clinical examination findings. The animals were randomly divided into study and control groups. The LMSC group (n = 10) received LMSCs (at least 2×106 cells) cultured on contact lenses. The conventional treatment group (n = 10) received artificial tears, topical 0.05% Cs A, and antibiotic eye drops, 3 times a day for 4 weeks. The Schirmer test, tear break-up time, impression cytology, Rose Bengal staining, and tear osmolarity were measured in all patients. The findings of the pre-treatment, two weeks and four weeks after the treatment, were evaluated statistically. In both groups, significant improvement was present compared to the pre-treatment findings. However, there was no significant difference between the groups. KCS treatment using LMSCs produced on contact lenses is promising, with its ease of application, non-immunogenic properties and single dose administration.
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Xie, Tao, Yao Li, Shi-Lei Li, and Hai-Feng Luo. "Astragaloside IV Enhances Cisplatin Chemosensitivity in Human Colorectal Cancer via Regulating NOTCH3." Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 24, no. 6 (October 27, 2016): 447–53. http://dx.doi.org/10.3727/096504016x14685034103590.
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Although astragaloside IV exhibits anti-inflammation, immunoregulatory, and anticancer properties, the chemosensitization effects of astragaloside IV in colorectal cancer have never been reported. Our study tested whether astragaloside could increase cisplatin sensitivity in colorectal cancer. CCK-8 assay was used to measure the cell viability of colorectal cancer cells. Quantitative real-time PCR and Western blot were performed to determine the mRNA and protein expression, respectively. Our data revealed that astragaloside IV administration significantly suppressed the cell growth of colorectal cancer cells, whereas no obvious cytotoxicity of astragaloside IV was observed in nonmalignant colonic cells. In addition, combined treatment with astragaloside IV dramatically elevated the chemosensitivity of colorectal cancer cells to cisplatin. Mechanical investigation revealed that the mRNA and protein expression of NOTCH3 was significantly lower in cisplatin and astragaloside IV-treated cells compared with cells treated with cisplatin alone. On the contrary, no obvious changes in tumor cell growth were shown after upregulation of NOTCH3 whether in the presence or absence of astragaloside IV. Thus, our data demonstrate that astragaloside IV increases the chemosensitivity of colorectal cancer cells to cisplatin, at least partly, through inhibition of NOTCH3. This study suggests that combined therapy with astragaloside IV might be a novel therapeutic approach for colorectal cancer.
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Li, Yaqian, Wenchen Cai, Fuyu Jin, Xiaojing Wang, Wenjing Liu, Tian Li, Xinyu Yang, Heliang Liu, Hong Xu, and Fang Yang. "Thalidomide Alleviates Pulmonary Fibrosis Induced by Silica in Mice by Inhibiting ER Stress and the TLR4-NF-κB Pathway." International Journal of Molecular Sciences 23, no. 10 (May 18, 2022): 5656. http://dx.doi.org/10.3390/ijms23105656.
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Silicosis is the most prevalent occupational disease in China. It is a form of pulmonary fibrosis caused by the inhalation of silicon particles. As there is no cure for the potentially lethal and progressive condition, the treatment of silicotic fibrosis is an important and difficult problem to address. Thalidomide, a drug with anti-inflammatory and immunoregulatory properties, has been reported to have lung-protective effects. The purpose of this study was to observe the therapeutic effect of thalidomide on silicotic mice and to determine the protective mechanism. By using silicotic mice models and MH-S cells, we found the expression of endoplasmic reticulum stress (ER stress) and Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) pathway as well as inflammation-related factors were upregulated in the macrophages of silicotic mice. The same indexes were detected in silica-stimulated MH-S cells, and the results were consistent with those in vivo. That is, silica activated ER stress and the TLR4-NF-κB pathway as well as the inflammatory response in vitro. Treating both silicotic mice and silica-stimulated MH-S cells with thalidomide inhibited ER stress and the TLR4-NF-κB pathway as well as the inflammatory response. The present study demonstrates thalidomide as a potential therapeutic agent against silicosis.
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Khan, Muhammad Zahoor, Yulin Ma, Jianxin Xiao, Tianyu Chen, Jiaying Ma, Shuai Liu, Yajing Wang, Adnan Khan, Gibson Maswayi Alugongo, and Zhijun Cao. "Role of Selenium and Vitamins E and B9 in the Alleviation of Bovine Mastitis during the Periparturient Period." Antioxidants 11, no. 4 (March 29, 2022): 657. http://dx.doi.org/10.3390/antiox11040657.
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Mastitis (inflammation of the mammary gland) commonly occurs in dairy cattle during the periparturient period (transition period), in which dairy cattle experience physiological and hormonal changes and severe negative energy balance, followed by oxidative stress. To maintain successful lactation and combat negative energy balance (NEB), excessive fat mobilization occurs, leading to overproduction of reactive oxygen species (ROS). Excessive fat mobilization also increases the concentrations of nonesterified fatty acids (NEFA) and β-hydroxybutyric acid (BHB) during the periparturient period. In addition, the excessive utilization of oxygen by cellular respiration in the mammary causes abnormal production of oxidative stress (OS). OS impairs the immunity and anti-inflammatory efficiency of periparturient dairy cattle, increasing their susceptibility to mastitis. To alleviate oxidative stress and subsequent mastitis, antioxidants are supplemented to dairy cattle from an external source. Extensive studies have been conducted on the supplementation of selenium (Se) and vitamins E and B9 to mitigate mastitis during the transition period in dairy cattle. Altogether, in the current review, we discuss the research development on bovine mastitis and its major causes, with special emphasis on oxidative stress during the transition period. Moreover, we discuss the antioxidant, immunoregulatory, and anti-inflammatory properties of Se and vitamins E and B9 and their role in the control of bovine mastitis in periparturient dairy cattle.
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Tocheva, Anna S., Michael Peled, Shruti Nayak, Elliot A. Philips, Beatrix Ueberheide, and Adam Mor. "Global phosphoproteomic analysis of PD-1 signaling reveals T cell subset specific PD-1 functions." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 112.6. http://dx.doi.org/10.4049/jimmunol.200.supp.112.6.
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Abstract PD-1 is a cell surface receptor with immunoregulatory properties expressed in activated T cells. PD-1 binds to either PD-L1 or PD-L2 and mediates downstream tyrosine dephosphorylation of key proteins critical for TCR signaling. This prevents excessive inflammation as well as T cell mediated anti-tumor immunity. Anti-PD-1 therapy is effective in ~30% of cancer patients, of which up to 25% develop off-target immune inflammation. Little is known about downstream signaling triggered by PD-1 and further analysis will provide better rationales for safer and more effective PD-1 targeting therapies. We performed tandem mass tag spectrometry and examined protein phosphorylation in Jurkat T cells following PD-1 ligation by PD-L2. Computational analysis revealed the PD-1/PD-L2 phosphoproteomic landscape. Our results confirm previous reports that PD-1 ligation dephosphorylates key proteins in the TCR signaling cascade. In addition, compared to unstimulated cells and to cells stimulated via the TCR alone, αCD3 stimulation in the presence of PD-1 ligation led to significant dephosphorylation of proteins involved in cytoskeletal organization and cellular adhesion. Surprisingly, we observed increased S/T phosphorylation of proteins associated with cell cycle regulation, chromosomal organization and negative regulation of gene expression triggered by PD-1 ligation. Further analysis in primary human cells revealed that these PD-1 triggered pathways were T cell subset specific, which is key for developing T cell subset specific targeted therapies. Our study provides a comprehensive system wide view of the signaling cascade downstream of PD-1 and may serve as a springboard for future therapeutic approaches targeting the PD-1 pathway.
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Shen, Chao-Bin, Yan-Ni Gu, Song Wang, and Lan Yu. "Astragaloside IV, the major bioactive component of Astragalus membranaceus (Fisch.) Radix, attenuates airway inflammation by modulating Th2 cytokines, STAT6 and ROR-γτ transcription factors in an asthmatic mouse model." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 183.6. http://dx.doi.org/10.4049/jimmunol.202.supp.183.6.
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Abstract OBJECTIVE Astragaloside IV (AS-IV), the major bioactive component of Astragalus membranaceus (Fisch.) Radix, possesses anti-inflammatory, regular immunological balance and other pharmacological properties. Although Astragalus is associated with immunoregulatory functions of allergic diseases, the pathophysiological mechanisms of AS-IV action in allergic inflammatory lung disease have not been examined. This study aims to explore the mechanisms of how AS-IV suppresses airway inflammation in bronchial asthma by inhibiting the inflammatory cytokines and transcription factors pathway. METHODS A total of 40 BALB/c male mice were selected and divided into control, asthma, AS-IV and dexamethasone groups. Ovalbumin-induced mouse asthma model was established. HE staining were conducted to observe the pulmonary pathological changes. ELISA was adopted for the levels of IFN-γ, IL-5, IL-13, IL-17A and TGF-β, qRT-PCR for the transcription factors mRNA expressions of GATA-3, STAT6, T-bet, RORγt, and Foxp3. RESULTS Compared with the control group, the asthma group had irregular tissue structure and severe inflammation, increases in maximal pulmonary resistance. AS-IV strongly suppressed levels of Th2 cytokines IL-5 and IL-13 in lung homogenate, but it upregulated T-bet and Foxp-3 mRNA expression in lungs. AS-IV exerted immunomodulatory effects through downregulation of STAT6, RORγt and GATA-3 expression. CONCLUSION These results suggest that the anti-asthmatic activity of AS-IV may occur by the suppression of IL-5, and IL-13 production through inhibition of the STAT6 and RORγt signaling pathways. Our results suggest that AS-IV can be a novel therapeutic component for the treatment of allergic asthma.
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Rola-Pleszczynski, M., C. Pouliot, S. Turcotte, B. Pignol, P. Braquet, and L. Bouvrette. "Immune regulation by platelet-activating factor. I. Induction of suppressor cell activity in human monocytes and CD8+ T cells and of helper cell activity in CD4+ T cells." Journal of Immunology 140, no. 10 (May 15, 1988): 3547–52. http://dx.doi.org/10.4049/jimmunol.140.10.3547.
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Abstract Platelet-activating factor (PAF) is a powerful mediator of inflammation. We have recently described a potential role for PAF in immune reactions, as it inhibits T cell proliferation and IL-2 production in response to mitogens. To further define the mechanism through which this inhibition is exerted, we used a coculture system in which PBML are preincubated with increasing concentrations of PAF for 24 h, followed by washing, treatment with mitomycin C and addition to fresh autologous PBML stimulated with PHA. In this context, a significant (40 to 60%) inhibition of proliferation was observed. In parallel, PAF-pre-treated cells induced a reduction (30 to 50%) of IL-2 production by PHA-stimulated lymphocytes. The PAF receptor antagonist BN52021 could partially block the PAF-induced suppressor cell activity, but also showed some suppressor cell-inducing properties of its own (20 to 30%). The expression of suppressor cell function during the co-culture could be partially abrogated by the inclusion of indomethacin, suggesting that cycloxygenase metabolites of arachidonic acid were involved in this phase of suppression. When PBML were fractionated into monocytes, lymphocytes, or T cell subsets before pre-incubation with PAF, indomethacin-sensitive suppressor cell function was generated in the monocyte population. Monocyte-depleted lymphocytes showed slight helper effect, whereas CD8+ T cells were induced to become indomethacin-resistant suppressor cells. CD4+ T cells, in contrast, were activated to exert very marked helper effect. When incubated with PAF for 24 h, monocyte-depleted lymphocytes showed a 30% decrease in CD4+ T cell numbers and a 50% increase in CD8+ T cell numbers. Our data suggest a novel immunoregulatory role for PAF and potentially important interactions of this lipid mediator of inflammation with lymphocyte and monocyte functions.
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Yadav, Vipul, Yang Mai, Laura E. McCoubrey, Yasufumi Wada, Motoyasu Tomioka, Satofumi Kawata, Shrikant Charde, and Abdul W. Basit. "5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease." Biomedicines 9, no. 5 (May 20, 2021): 578. http://dx.doi.org/10.3390/biomedicines9050578.
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5-Aminolevulinic acid (5-ALA) is a naturally occurring nonprotein amino acid licensed as an optical imaging agent for the treatment of gliomas. In recent years, 5-ALA has been shown to possess anti-inflammatory and immunoregulatory properties through upregulation of heme oxygenase-1 via enhancement of porphyrin, indicating that it may be beneficial for the treatment of inflammatory conditions. This study systematically examines 5-ALA for use in inflammatory bowel disease (IBD). Firstly, the ex vivo colonic stability and permeability of 5-ALA was assessed using human and mouse fluid and tissue. Secondly, the in vivo efficacy of 5-ALA, in the presence of sodium ferrous citrate, was investigated via the oral and intracolonic route in an acute DSS colitis mouse model of IBD. Results showed that 5-ALA was stable in mouse and human colon fluid, as well as in colon tissue. 5-ALA showed more tissue restricted pharmacokinetics when exposed to human colonic tissue. In vivo dosing demonstrated significantly improved colonic inflammation, increased local heme oxygenase-1 levels, and decreased concentrations of proinflammatory cytokines TNF-α, IL-6, and IL-1β in both plasma and colonic tissue. These effects were superior to that measured concurrently with established anti-inflammatory treatments, ciclosporin and 5-aminosalicylic acid (mesalazine). As such, 5-ALA represents a promising addition to the IBD armamentarium, with potential for targeted colonic delivery.
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Chyuan, I.-Tsu, Hong-Tai Tzeng, and Ji-Yih Chen. "Signaling Pathways of Type I and Type III Interferons and Targeted Therapies in Systemic Lupus Erythematosus." Cells 8, no. 9 (August 23, 2019): 963. http://dx.doi.org/10.3390/cells8090963.
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Type I and type III interferons (IFNs) share several properties in common, including the induction of signaling pathways, the activation of gene transcripts, and immune responses, against viral infection. Recent advances in the understanding of the molecular basis of innate and adaptive immunity have led to the re-examination of the role of these IFNs in autoimmune diseases. To date, a variety of IFN-regulated genes, termed IFN signature genes, have been identified. The expressions of these genes significantly increase in systemic lupus erythematosus (SLE), highlighting the role of type I and type III IFNs in the pathogenesis of SLE. In this review, we first discussed the signaling pathways and the immunoregulatory roles of type I and type III IFNs. Next, we discussed the roles of these IFNs in the pathogenesis of autoimmune diseases, including SLE. In SLE, IFN-stimulated genes induced by IFN signaling contribute to a positive feedback loop of autoimmunity, resulting in perpetual autoimmune inflammation. Based on this, we discussed the use of several specific IFN blocking strategies using anti-IFN-α antibodies, anti-IFN-α receptor antibodies, and IFN-α-kinoid or downstream small molecules, which intervene in Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways, in clinical trials for SLE patients. Hopefully, the development of novel regimens targeting IFN signaling pathways will shed light on promising future therapeutic applications for SLE patients.
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Tortora, Chiara, Alessandra Di Paola, Maura Argenziano, Mara Creoli, Maria Maddalena Marrapodi, Sabrina Cenni, Carlo Tolone, Francesca Rossi, and Caterina Strisciuglio. "Effects of CB2 Receptor Modulation on Macrophage Polarization in Pediatric Celiac Disease." Biomedicines 10, no. 4 (April 9, 2022): 874. http://dx.doi.org/10.3390/biomedicines10040874.
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Celiac Disease (CD) represents an autoimmune disorder triggered by the exposure to gluten in genetically susceptible individuals. Recent studies suggest the involvement of macrophages in CD pathogenesis. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). The Cannabinoid Receptor 2 (CB2) has important anti-inflammatory and immunoregulatory properties. We previously demonstrated that a common CB2 functional variant, Q63R, causing CB2 reduced function, is associated with several inflammatory and autoimmune diseases The first aim of this study was to investigate the phenotype of macrophages isolated from peripheral blood of CD patients and CB2 expression. The second aim was to evaluate the effects of CB2 pharmacological modulation on CD macrophage polarization. Moreover, by an in vitro model of “immunocompetent gut” we investigated the role of CD macrophages in inducing intestinal barrier damage and the possibility to restore its functionality modulating their polarization. We found an increased expression of M1 macrophages and a CB2 reduced expression. We also demonstrated CD M1 macrophages in inducing the typical mucosal barrier damage of CD. CB2 stimulation switches macrophage polarization towards the anti-inflammatory M2 phenotype thus reducing inflammation but also limiting the epithelial dysfunction. Therefore, we suggest CB2 receptor as a possible novel therapeutic target for CD by regulating macrophages polarization and by preventing mucosal barrier damage.