Journal articles on the topic 'Tumor necrosis factor Physiological effect'
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1
Todorov, Vladimir, Markus Müller, Frank Schweda, and Armin Kurtz. "Tumor necrosis factor-α inhibits renin gene expression." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 283, no. 5 (November 1, 2002): R1046—R1051. http://dx.doi.org/10.1152/ajpregu.00142.2002.
Abstract:
Renin, produced in renal juxtaglomerular (JG) cells, is a fundamental regulator of blood pressure. Accumulating evidence suggests that cytokines may directly influence renin production in the JG cells. TNF-α, which is one of the key mediators in immunity and inflammation, is known to participate in the control of vascular proliferation and contraction and hence in the pathogenesis of cardiovascular diseases. Thus TNF-α may exert its effects on the cardiovascular system through modulation of renal renin synthesis. Therefore we have tested the effect of TNF-α on renin transcription in As4.1 cells, which represent transformed mouse JG cells, and in native mouse JG cells in culture. Renin gene expression was also determined in mice lacking the gene for TNF-α (TNF-α knockout mice). TNF-α inhibited renin gene expression via an inhibition of the transcriptional activity, targeting the proximal 4.1 kb of the renin promoter in As4.1 cells. TNF-α also attenuated forskolin-stimulated renin gene expression in primary cultures of mouse JG cells. Mice lacking the TNF-α gene had almost threefold higher basal renal renin mRNA abundance relative to the control strain. The general physiological regulation of renin expression by salt was not disturbed in TNF-α knockout mice. Our data suggest that TNF-α inhibits renin gene transcription at the cellular level and thus may act as a modulator of renin synthesis in (physio)pathological situations.
2
Greenberg, S., J. Xie, Y. Wang, B. Cai, J. Kolls, S. Nelson, A. Hyman, W. R. Summer, and H. Lippton. "Tumor necrosis factor-alpha inhibits endothelium-dependent relaxation." Journal of Applied Physiology 74, no. 5 (May 1, 1993): 2394–403. http://dx.doi.org/10.1152/jappl.1993.74.5.2394.
Abstract:
Tumor necrosis factor-alpha (TNF-alpha) stimulates nitric oxide (NO) in vascular endothelium by induction of the enzyme NO synthase II (NOS II). We examined the effects of TNF-alpha on 1) endothelium-dependent (EDR) and endothelium-independent (EIR) relaxation and 2) contraction of bovine intralobar pulmonary arteries (BPA) and veins (BPV) in vitro. Acetylcholine (ACh), bradykinin (BK), histamine, and A23187 produced EDR of BPA contracted with a 50% effective concentration of U-46619 (15 nM), because relaxation was abolished by endothelium-rubbing and attenuated by L-NG-mono-methylarginine (L-NMMA; 300 microM). TNF-alpha (0.00417, 0.0417, 0.417, and 1.25 micrograms/ml) incubated with BPA for 60 min inhibited EDR of the BPA to ACh, BK, and histamine. The effects of TNF required 30 min for onset. Recovery of EDR occurred 3–4 h after washout of TNF-alpha. Pentoxifylline (1 microM) did not affect ACh-induced EDR but selectively reversed TNF-alpha-mediated inhibition of ACh-induced EDR. TNF-alpha-mediated inhibition of EDR was not reversible by L-NMMA, an inhibitor of NOS I and NOS II, the cyclooxygenase inhibitor ibuprofen, or CV-3908 (1 microM), a platelet-activating factor antagonist. The inhibitory effect of TNF-alpha on EDR was not mediated by nonspecific sensitization of the endothelium to human protein because recombinant human granulocyte colony-stimulating factor (10, 50, and 500 x 10(3) U/ml) did not affect EDR of BPA. The effect of TNF-alpha was specific for release of NO from the endothelium of BPA because TNF-alpha did not affect 1) EDR of BPV to ACh, BK, or ATP; 2) EIR of BPA or BPV to nitroprusside; and 3) contraction of either BPA or BPV to KCl, U-46619, histamine, norepinephrine, or serotonin. Thus TNF-alpha appears to selectively inhibit receptor-mediated EDR and NO release in BPA. TNF-alpha-mediated inhibition of EDR differs from that of L-arginine-based inhibitors and may represent an endogenous physiological mechanism of regulation of NO in the endothelium.
3
Moller, A. D., and P. O. Grande. "Low-dose prostacyclin has potent capillary permeability-reducing effect in cat skeletal muscle in vivo." American Journal of Physiology-Heart and Circulatory Physiology 273, no. 1 (July 1, 1997): H200—H207. http://dx.doi.org/10.1152/ajpheart.1997.273.1.h200.
Abstract:
The dose-response effects of intravenous infusion of prostacyclin on capillary permeability (the capillary filtration coefficient technique), hydrostatic capillary pressure, transcapillary filtration, and vascular tone were analyzed in vivo on cat skeletal muscle from a normal and an increased permeability level. Increased permeability was accomplished by intra-arterial infusion of tumor necrosis factor-alpha or histamine. Permeability effects of bradykinin were also analyzed. Prostacyclin decreased capillary permeability by 8% at a dose of 0.1 ng.kg-1.min-1 and at most by 30% below control attained at 2 ng.kg-1.min-1, also with no effect on vascular tone and hydrostatic capillary pressure. The permeability increase by tumor necrosis factor-alpha and histamine (by 54 and 73%) was more than counteracted by the simultaneous infusion of prostacyclin at 2 ng.kg-1.min-1. The vasodilator effect of tumor necrosis factor-alpha was also restituted. Indomethacin (prostacyclin inhibitor)-induced increase in capillary permeability (25%) was more than restituted by prostacyclin at 2 ng.kg-1.min-1. Surprisingly, bradykinin decreased capillary permeability. We conclude that endogenous prostacyclin may be a physiological regulator of capillary permeability and that low-dose prostacyclin infusion may have clinical relevance in states of increased permeability.
4
Alexander, H. R., G. G. Wong, G. M. Doherty, D. J. Venzon, D. L. Fraker, and J. A. Norton. "Differentiation factor/leukemia inhibitory factor protection against lethal endotoxemia in mice: synergistic effect with interleukin 1 and tumor necrosis factor." Journal of Experimental Medicine 175, no. 4 (April 1, 1992): 1139–42. http://dx.doi.org/10.1084/jem.175.4.1139.
Abstract:
Differentiation factor (D factor), also called leukemia inhibitory factor (LIF), is a glycoprotein that has been increasingly recognized to possess a wide range of physiological activities. We examined the possibility that the administration of D factor may confer beneficial effects and enhance host resistance against lethal endotoxemia. A single intravenous dose of recombinant human D factor completely protected C57/Bl6 mice from the lethal effect of Escherichia coli endotoxin (lipopolysaccharide [LPS]). The protective effects were dose dependent and observed when administered 2-24 h before LPS. Previous work has shown that interleukin 1 (IL-1) and tumor necrosis factor (TNF) also protect against a subsequent LPS challenge in a dose-dependent manner. When human D factor was combined with sub-protective doses of IL-1 beta or TNF-alpha, there was dramatic synergistic protection against a subsequent lethal LPS challenge.
5
Takahashi, Satoshi, Levente Kapás, Jidong Fang, and James M. Krueger. "Somnogenic relationships between tumor necrosis factor and interleukin-1." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 276, no. 4 (April 1, 1999): R1132—R1140. http://dx.doi.org/10.1152/ajpregu.1999.276.4.r1132.
Abstract:
Both tumor necrosis factor (TNF) and interleukin (IL)-1 are somnogenic cytokines. They also induce each other’s production and both induce nuclear factor kappa B activation, which in turn enhances IL-1 and TNF transcription. We hypothesized that TNF and IL-1 could influence each other’s somnogenic actions. To test this hypothesis, we determined the effects of blocking both endogenous TNF and IL-1 on spontaneous sleep and on sleep rebound after sleep deprivation in rabbits. Furthermore, the effects of inhibition of TNF on IL-1-induced sleep and the effects of blocking IL-1 on TNF-induced sleep were determined. A TNF receptor fragment (TNFRF), as a TNF inhibitor, and an IL-1 receptor fragment (IL-1RF), as an IL-1 inhibitor, were used. Intracerebroventricular injection of a combination of the TNFRF plus the IL-1RF significantly reduced spontaneous non-rapid eye movement sleep by 87 min over a 22-h recording period. Pretreatment of rabbits with the combination of TNFRF and IL-1RF also significantly attenuated sleep rebound after sleep deprivation. Furthermore, the TNFRF significantly attenuated IL-1-induced sleep but not fever. Finally, the IL-1RF blocked TNF-induced sleep responses but not fever. Results indicate that TNF and IL-1 cooperate to regulate physiological sleep.
6
Tseng, Wei-Cheng, Hou-Chuan Lai, Yi-Hsuan Huang, Shun-Ming Chan, and Zhi-Fu Wu. "Tumor Necrosis Factor Alpha: Implications of Anesthesia on Cancers." Cancers 15, no. 3 (January 25, 2023): 739. http://dx.doi.org/10.3390/cancers15030739.
Abstract:
Cancer remains a major public health issue and a leading cause of death worldwide. Despite advancements in chemotherapy, radiation therapy, and immunotherapy, surgery is the mainstay of cancer treatment for solid tumors. However, tumor cells are known to disseminate into the vascular and lymphatic systems during surgical manipulation. Additionally, surgery-induced stress responses can produce an immunosuppressive environment that is favorable for cancer relapse. Up to 90% of cancer-related deaths are the result of metastatic disease after surgical resection. Emerging evidence shows that the interactions between tumor cells and the tumor microenvironment (TME) not only play decisive roles in tumor initiation, progression, and metastasis but also have profound effects on therapeutic efficacy. Tumor necrosis factor alpha (TNF-α), a pleiotropic cytokine contributing to both physiological and pathological processes, is one of the main mediators of inflammation-associated carcinogenesis in the TME. Because TNF-α signaling may modulate the course of cancer, it can be therapeutically targeted to ameliorate clinical outcomes. As the incidence of cancer continues to grow, approximately 80% of cancer patients require anesthesia during cancer care for diagnostic, therapeutic, or palliative procedures, and over 60% of cancer patients receive anesthesia for primary surgical resection. Numerous studies have demonstrated that perioperative management, including surgical manipulation, anesthetics/analgesics, and other supportive care, may alter the TME and cancer progression by affecting inflammatory or immune responses during cancer surgery, but the literature about the impact of anesthesia on the TNF-α production and cancer progression is limited. Therefore, this review summarizes the current knowledge of the implications of anesthesia on cancers from the insights of TNF-α release and provides future anesthetic strategies for improving oncological survival.
7
Ramseyer, Vanesa D., and Jeffrey L. Garvin. "Tumor necrosis factor-α: regulation of renal function and blood pressure." American Journal of Physiology-Renal Physiology 304, no. 10 (May 15, 2013): F1231—F1242. http://dx.doi.org/10.1152/ajprenal.00557.2012.
Abstract:
Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that becomes elevated in chronic inflammatory states such as hypertension and diabetes and has been found to mediate both increases and decreases in blood pressure. High levels of TNF-α decrease blood pressure, whereas moderate increases in TNF-α have been associated with increased NaCl retention and hypertension. The explanation for these disparate effects is not clear but could simply be due to different concentrations of TNF-α within the kidney, the physiological status of the subject, or the type of stimulus initiating the inflammatory response. TNF-α alters renal hemodynamics and nephron transport, affecting both activity and expression of transporters. It also mediates organ damage by stimulating immune cell infiltration and cell death. Here we will summarize the available findings and attempt to provide plausible explanations for such discrepancies.
8
Salama, Salama A., Marwa W. Kamel, Concepcion R. Diaz-Arrastia, Xia Xu, Timothy D. Veenstra, Sana Salih, Shaleen K. Botting, and Raj Kumar. "Effect of Tumor Necrosis Factor-α on Estrogen Metabolism and Endometrial Cells: Potential Physiological and Pathological Relevance." Journal of Clinical Endocrinology & Metabolism 94, no. 1 (January 1, 2009): 285–93. http://dx.doi.org/10.1210/jc.2008-1389.
9
Wang, Chen, Yuchen Wang, Na Liu, Chuan Cai, and Lulu Xu. "Effect of tumor necrosis factor α on ability of SHED to promote osteoclastogenesis during physiological root resorption." Biomedicine & Pharmacotherapy 114 (June 2019): 108803. http://dx.doi.org/10.1016/j.biopha.2019.108803.
10
Matsumoto, Yutaka, Yohko Kawai, Kiyoaki Watanabe, Kazuo Sakai, Mitsuru Murata, Makoto Handa, Shin Nakamura, and Yasuo Ikeda. "Fluid Shear Stress Attenuates Tumor Necrosis Factor-α–Induced Tissue Factor Expression in Cultured Human Endothelial Cells." Blood 91, no. 11 (June 1, 1998): 4164–72. http://dx.doi.org/10.1182/blood.v91.11.4164.
Abstract:
Abstract Hemodynamic forces modulate various endothelial cell functions under gene regulation. Previously, we have shown that fibrinolytic activity of endothelial cells is enhanced by the synergistic effects of shear stress and cytokines. In this study, we investigated the effect of shear stress on tumor necrosis factor (TNF)-α–induced tissue factor (TF) expression in cultured human umbilical vein endothelial cells (HUVECs), using a modified cone-plate viscometer. Shear stresses at physiological levels reduced TNF-α (100 U/mL)–induced TF expression at both mRNA and antigen levels, in a shear-intensity and exposure-time dependent manner, whereas shear stress itself did not induce TF expression in HUVECs. TF expressed on the cell surfaces measured by flow cytometry using an anti-TF monoclonal antibody (HTF-K180) was also decreased to one third by shear force applied at 18 dynes/cm2 for 15 hours before and 6 hours after TNF-α stimulation. Furthermore, functional activity of TF, as assessed by the activation of factor X in the presence of FVIIa and Ca2+, was also decreased by shear application. However, the stability of TF mRNA was not decreased in the presence of shear stress. These results suggest that shear force acts as an important regulator of TF expression in endothelium at the transcriptional level.
11
Matsumoto, Yutaka, Yohko Kawai, Kiyoaki Watanabe, Kazuo Sakai, Mitsuru Murata, Makoto Handa, Shin Nakamura, and Yasuo Ikeda. "Fluid Shear Stress Attenuates Tumor Necrosis Factor-α–Induced Tissue Factor Expression in Cultured Human Endothelial Cells." Blood 91, no. 11 (June 1, 1998): 4164–72. http://dx.doi.org/10.1182/blood.v91.11.4164.411k29_4164_4172.
Abstract:
Hemodynamic forces modulate various endothelial cell functions under gene regulation. Previously, we have shown that fibrinolytic activity of endothelial cells is enhanced by the synergistic effects of shear stress and cytokines. In this study, we investigated the effect of shear stress on tumor necrosis factor (TNF)-α–induced tissue factor (TF) expression in cultured human umbilical vein endothelial cells (HUVECs), using a modified cone-plate viscometer. Shear stresses at physiological levels reduced TNF-α (100 U/mL)–induced TF expression at both mRNA and antigen levels, in a shear-intensity and exposure-time dependent manner, whereas shear stress itself did not induce TF expression in HUVECs. TF expressed on the cell surfaces measured by flow cytometry using an anti-TF monoclonal antibody (HTF-K180) was also decreased to one third by shear force applied at 18 dynes/cm2 for 15 hours before and 6 hours after TNF-α stimulation. Furthermore, functional activity of TF, as assessed by the activation of factor X in the presence of FVIIa and Ca2+, was also decreased by shear application. However, the stability of TF mRNA was not decreased in the presence of shear stress. These results suggest that shear force acts as an important regulator of TF expression in endothelium at the transcriptional level.
12
Moxey-Mims, M. M., H. H. Simms, M. M. Frank, E. Y. Lin, and T. A. Gaither. "The effects of IL-1, IL-2, and tumor necrosis factor on polymorphonuclear leukocyte Fc gamma receptor-mediated phagocytosis. IL-2 down-regulates the effect of tumor necrosis factor." Journal of Immunology 147, no. 6 (September 15, 1991): 1823–30. http://dx.doi.org/10.4049/jimmunol.147.6.1823.
Abstract:
Abstract It has been reported that the Fc gamma R-mediated phagocytic activity of polymorphonuclear leukocytes (PMN) from patients with acute bacterial infections is markedly enhanced when compared with healthy controls. Inasmuch as several potent cytokines are known to be involved in inflammatory and infectious processes, we studied the effects of three such cytokines (IL-1 beta, IL-2, and TNF-alpha) on normal PMN Fc gamma R-mediated phagocytosis. IL-1 beta and TNF alpha both caused a significant increase in the ingestion of EIgG by adherent PMN. In combination, IL-1 beta and TNF-alpha had an additive effect, even when each was used at its optimal concentration. In contrast to the enhancing effects mediated by IL-1 beta and TNF-alpha, IL-2 alone had no significant effect on PMN phagocytosis. Notably, however, IL-2 at a concentration of 10(4) U/ml partially inhibited TNF-alpha-mediated enhancement of phagocytosis by decreasing TNF binding to the PMN cell surface. This inhibitory effect of IL-2 on TNF was reversed by anti-IL-2 antibody and mAb directed against the low affinity IL-2R (anti-Tac), whereas mAb directed against the intermediate affinity receptor (mik-beta 1) had no such effect. These findings may have important physiologic implications, because patients receiving IL-2 therapy have been shown to have increased susceptibility to infection.
13
Tachimoto, Hiroshi, and Motohiro Ebisawa. "Effect of Interleukin-13 or Tumor Necrosis Factor-Alpha on Eosinophil Adhesion to Endothelial Cells under Physiological Flow Conditions." International Archives of Allergy and Immunology 143, no. 1 (2007): 33–37. http://dx.doi.org/10.1159/000101402.
14
Alpini, Gianfranco, Yoshiyuki Ueno, Laura Tadlock, Shannon S. Glaser, Gene LeSage, Heather Francis, Silvia Taffetani, Marco Marzioni, Domenico Alvaro, and Tushar Patel. "Increased susceptibility of cholangiocytes to tumor necrosis factor-α cytotoxicity after bile duct ligation." American Journal of Physiology-Cell Physiology 285, no. 1 (July 2003): C183—C194. http://dx.doi.org/10.1152/ajpcell.00497.2002.
Abstract:
Tumor necrosis factor (TNF)-α plays a critical role in epithelial cell injury. However, the role of TNF-α in mediating cholangiocyte injury under physiological or pathophysiological conditions is unknown. Thus we assessed the effects of TNF-α alone or following sensitization by actinomycin D on cell apoptosis, proliferation, and basal and secretin-stimulated ductal secretion in cholangiocytes from normal or bile duct-ligated (BDL) rats. Cholangiocytes from normal or BDL rats were highly resistant to TNF-α alone. However, presensitization by actinomycin D increased apoptosis in cholangiocytes following BDL and was associated with an inhibition of proliferation and secretin-stimulated ductal secretion. Thus TNF-α mediates cholangiocyte injury and altered ductal secretion following bile duct ligation. These observations suggest that cholestasis may enhance susceptibility to cytokine-mediated cholangiocyte injury.
15
Markova, T. N., N. K. Mishchenko, and D. V. Petina. "Adipocytokines: modern definition, classification and physiological role." Problems of Endocrinology 68, no. 1 (December 6, 2021): 73–80. http://dx.doi.org/10.14341/probl12805.
Abstract:
Adipose tissue is an endocrine organ which produces a large number of secretory bioactive substances also known as adipocytokines affecting directly insulin resistance (IR), glucose and lipid metabolism, angiogenesis and inflammation. The studies show a close connection between the imbalance of adipocytokines formed as a result of excessive deposit of adipose tissue in the course of the development of type 2 diabetes mellitus and cardiovascular diseases. In the present review, we summarize current data on the effect of the adipocytokines on the liver, skeletal muscles, adipose tissue, endothelial cells and inflammatory processes, as well as attempt to define the term «adipocytokines» and classify adipocytokines according to their influence on metabolic processes and pro-inflammatory status. Some of adipocytokines (adiponectin, omentin, leptin, resistin, tumor necrosis factor-α and interleukin-6) are divided into two groups: adipocytokines reducing IR, and adipocytokines increasing IR.
16
Guarnieri, Giulia, Erica Sarchielli, Paolo Comeglio, Erika Herrera-Puerta, Irene Piaceri, Benedetta Nacmias, Matteo Benelli, et al. "Tumor Necrosis Factor α Influences Phenotypic Plasticity and Promotes Epigenetic Changes in Human Basal Forebrain Cholinergic Neuroblasts." International Journal of Molecular Sciences 21, no. 17 (August 25, 2020): 6128. http://dx.doi.org/10.3390/ijms21176128.
Abstract:
TNFα is the main proinflammatory cytokine implicated in the pathogenesis of neurodegenerative disorders, but it also modulates physiological functions in both the developing and adult brain. In this study, we investigated a potential direct role of TNFα in determining phenotypic changes of a recently established cellular model of human basal forebrain cholinergic neuroblasts isolated from the nucleus basalis of Meynert (hfNBMs). Exposing hfNBMs to TNFα reduced the expression of immature markers, such as nestin and β-tubulin III, and inhibited primary cilium formation. On the contrary, TNFα increased the expression of TNFα receptor TNFR2 and the mature neuron marker MAP2, also promoting neurite elongation. Moreover, TNFα affected nerve growth factor receptor expression. We also found that TNFα induced the expression of DNA-methylation enzymes and, accordingly, downregulated genes involved in neuronal development through epigenetic mechanisms, as demonstrated by methylome analysis. In summary, TNFα showed a dual role on hfNBMs phenotypic plasticity, exerting a negative influence on neurogenesis despite a positive effect on differentiation, through mechanisms that remain to be elucidated. Our results help to clarify the complexity of TNFα effects in human neurons and suggest that manipulation of TNFα signaling could provide a potential therapeutic approach against neurodegenerative disorders.
17
Ravid, A., E. Rubinstein, A. Gamady, C. Rotem, UA Liberman, and R. Koren. "Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes." Journal of Endocrinology 173, no. 3 (June 1, 2002): 525–32. http://dx.doi.org/10.1677/joe.0.1730525.
Abstract:
In addition to its known effects on keratinocyte proliferation and differentiation, the hormonal form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been shown to protect keratinocytes from UV- and chemotherapy-induced damage. Epidermal keratinocytes contain both the machinery needed to produce 1,25(OH)(2)D(3) and vitamin D receptors. The activation of the stress-activated protein kinases (SAPKs), such as c-Jun N-terminal kinase (JNK) and p38, is an early cellular response to stress signals and an important determinant of cell fate. This study examines whether modulation of these SAPKs is associated with the effects of 1,25(OH)(2)D(3) on keratinocytes under stress. HaCaT keratinocytes were exposed to heat shock, hyperosmotic concentrations of sorbitol, the epidermal growth factor receptor tyrosine kinase inhibitor AG1487, the pro-inflammatory cytokine tumor necrosis factor alpha, and H(2)O(2). These stresses activated both SAPKs. Pretreatment with 1,25(OH)(2)D(3) inhibited the activation of JNK by all stresses and the activation of p38 by heat shock, AG1478 and tumor necrosis factor alpha. Under the same conditions, treatment with 1,25(OH)(2)D(3) protected HaCaT keratinocytes from cytotoxicity induced by exposure to H(2)O(2) and hyperosmotic shock. The effect of 1,25(OH)(2)D(3) was dose-dependent, already apparent at nanomolar concentrations, and time-dependent, maximal after a 24-h pre-incubation. We suggest that inhibition of SAPK activation may account for some of the well-documented protective effects of 1,25(OH)(2)D(3) on epidermal cells during exposure to UV or chemotherapy and may also be related to the anti-inflammatory actions of the hormone in skin.
18
Pan, Weihong, Germaine Cornélissen, Franz Halberg, and Abba J. Kastin. "Selected Contribution: Circadian rhythm of tumor necrosis factor-α uptake into mouse spinal cord." Journal of Applied Physiology 92, no. 3 (March 1, 2002): 1357–62. http://dx.doi.org/10.1152/japplphysiol.00915.2001.
Abstract:
Circadian variations in the actions of tumor necrosis factor-α (TNF-α) have been observed. Because a saturable transport system at the blood-brain barrier mediates most of the influx of TNF-α from blood to the central nervous system (CNS), the circadian variation of the CNS effects of TNF-α could be related to changes in this transport system. Accordingly, we measured the uptake of intravenously injected TNF-α into various CNS regions at different times and compared these measurements with the uptake into a peripheral control (muscle). We found that the spinal cord, but not the brain, showed a circadian rhythm in the uptake of TNF-α. This pattern is similar to that of leptin but different from that of interleukin-1. The circadian rhythm of the influx of TNF-α into this region of the CNS suggests a functional role for the spinal cord in the physiological actions of TNF-α.
19
Otsuka, Y., K. Nagano, K. Nagano, K. Hori, J. Oh-ishi, H. Hayashi, N. Watanabe, and Y. Niitsu. "Inhibition of neutrophil migration by tumor necrosis factor. Ex vivo and in vivo studies in comparison with in vitro effect." Journal of Immunology 145, no. 8 (October 15, 1990): 2639–43. http://dx.doi.org/10.4049/jimmunol.145.8.2639.
Abstract:
Abstract Coincubation of neutrophils with TNF inhibited the chemoattractant-directed migration of neutrophils under agarose and enhanced their migration in the multiwell chemotaxis chamber. To assess the physiological significance of these differing in vitro TNF effects, ex vivo and in vivo investigations were performed using animal models. Neutrophils from the peripheral blood of rabbits preadministered systemic TNF showed impaired ability to migrate toward chemoattractants in vitro. In addition, systemic TNF administration suppressed zymosan-activated plasma-induced local accumulation of leukocytes in mouse skin. The results indicate that circulating TNF may act as a suppressor for local inflammatory reaction.
20
Yokochi, T., A. Kusumi, N. Kido, Y. Kato, T. Sugiyama, N. Koide, G. Z. Jiang, K. Narita, and K. Takahashi. "Differential release of smooth-type lipopolysaccharide from Pseudomonas aeruginosa treated with carbapenem antibiotics and its relation to production of tumor necrosis factor alpha and nitric oxide." Antimicrobial Agents and Chemotherapy 40, no. 10 (October 1996): 2410–12. http://dx.doi.org/10.1128/aac.40.10.2410.
Abstract:
Endotoxin release from Pseudomonas aeruginosa treated with cell wall-active carbapenem antibiotics and its effect on the production of tumor necrosis factor alpha and nitric oxide were examined. Treatment of bacteria with imipenem induced much lower levels of endotoxin release than treatment with meropenem. The endotoxin released was demonstrated to be of the smooth type and O-specific polysaccharide-rich. The exposure of the filtrates of P. aeruginosa treated with imipenem to physiologically relevant cells caused low-level production of tumor necrosis factor alpha and nitric oxide, while similar treatment with meropenem induced high levels of production.
21
Wilson, Michael R., Michael E. Goddard, Kieran P. O'Dea, Sharmila Choudhury, and Masao Takata. "Differential roles of p55 and p75 tumor necrosis factor receptors on stretch-induced pulmonary edema in mice." American Journal of Physiology-Lung Cellular and Molecular Physiology 293, no. 1 (July 2007): L60—L68. http://dx.doi.org/10.1152/ajplung.00284.2006.
Abstract:
Ventilator-induced lung injury plays a crucial role in the outcome of patients with acute lung injury. Previous studies have shown a role for the cytokine tumor necrosis factor-α (TNF) in stretch-induced alveolar neutrophil recruitment, but the involvement of TNF in stretch-induced pulmonary edema is unclear. We investigated the effects of TNF through its individual p55 and p75 receptors on early pulmonary edema formation during high stretch ventilation, before neutrophil infiltration. Anesthetized wild-type or TNF receptor single/double knockout mice were ventilated with high tidal volume (∼38 ml/kg) for 2 h or until they developed arterial hypotension. Pulmonary edema was assessed by physiological parameters including respiratory mechanics and blood gases, and by lavage fluid protein, lung wet:dry weight ratio, and lung permeability measurements using fluorescence-labeled albumin. High stretch ventilation in wild-type and TNF receptor double knockout animals induced similar pulmonary edema, and only 25–30% of mice completed the protocol. In contrast, the p55 receptor knockout mice were strongly protected from edema formation, with all animals completing the protocol. Myeloperoxidase assay indicated that this protective effect was not associated with decreased pulmonary neutrophil sequestration. The p75 receptor knockout mice, however, displayed increased susceptibility to edema formation, and no animals survived the full 2 h. These results demonstrate a novel role for TNF signaling (independent from its effects on neutrophil recruitment) specifically through the p55 receptor, in promoting high stretch-induced pulmonary edema, whereas p75 signaling may play an opposing role.
22
Kubota, Takeshi, Jidong Fang, Zhiwei Guan, Richard A. Brown, and James M. Krueger. "Vagotomy attenuates tumor necrosis factor-α-induced sleep and EEG δ-activity in rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 280, no. 4 (April 1, 2001): R1213—R1220. http://dx.doi.org/10.1152/ajpregu.2001.280.4.r1213.
Abstract:
Much evidence suggests that tumor necrosis factor-α (TNF-α) is involved in the regulation of physiological sleep. However, it remains unclear whether peripheral administration of TNF-α induces sleep in rats. Furthermore, the role of the vagus nerve in the somnogenic actions of TNF-α had not heretofore been studied. Four doses of TNF-α were administered intraperitoneally just before the onset of the dark period. The three higher doses of TNF-α (50, 100, and 200 μg/kg) dose dependently increased nonrapid eye movement sleep (NREMS), accompanied by increases in electroencephalogram (EEG) slow-wave activity. TNF-α increased EEG δ-power and decreased EEG α- and β-power during the initial 3 h after injection. In vagotomized rats, the NREMS responses to 50 or 100 μg/kg of TNF-α were attenuated, while significant TNF-α-induced increases in NREMS were observed in a sham-operated group. Moreover, the vagotomized rats failed to exhibit the increase in EEG δ-power induced by TNF-α intraperitoneally. These results suggest that peripheral TNF-α can induce NREMS and vagal afferents play an important role in the effects of peripheral TNF-α and EEG synchronization on sleep. Intraperitoneal TNF-α failed to affect brain temperature at the doses tested, thereby demonstrating that TNF-α-induced sleep effects are, in part, independent from its effects on brain temperature. Results are consistent with the hypothesis that a cytokine network is involved in sleep regulation.
23
Ensor, J. E., S. M. Wiener, K. A. McCrea, R. M. Viscardi, E. K. Crawford, and J. D. Hasday. "Differential effects of hyperthermia on macrophage interleukin-6 and tumor necrosis factor-alpha expression." American Journal of Physiology-Cell Physiology 266, no. 4 (April 1, 1994): C967—C974. http://dx.doi.org/10.1152/ajpcell.1994.266.4.c967.
Abstract:
The pyrogenic cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) appear in the circulation during infections and injuries, but TNF-alpha and IL-6 are regulated differently in macrophages. We compared the effects of elevated temperatures within the usual febrile range on the expression of TNF-alpha and IL-6 in vitro in lipopolysaccharide (LPS)-stimulated human macrophages derived from peripheral blood monocytes (HuMoM phi). During an 18-h incubation at 37 degrees C with 5 ng/ml LPS, these cells released 5,030 +/- 1,460 pg TNF-alpha/10(6) cells (means +/- SE) and 1,380 +/- 280 pg IL-6/10(6) cells. In LPS-stimulated HuMoM phi incubated at 40 degrees C, TNF-alpha release was almost completely inhibited (76 +/- 76 pg TNF-alpha/10(6) cells; P < 0.01 compared with LPS-stimulated HuMoM phi at 37 degrees C), but release of IL-6 was preserved (1,600 +/- 780 pg IL-6/10(6) cells). Western and Northern analyses showed that levels of TNF-alpha mRNA and cell-associated and secreted TNF-alpha protein were decreased, but IL-6 expression was unchanged at 40 degrees C in LPS-stimulated macrophages. Incubating HuMoM phi at 40 degrees did not alter their viability after 18 h but induced a 75-fold increase in levels of the inducible heat-shock protein 72 (HSP-72) mRNA in the face of a 56% inhibition in total protein synthesis. Our results show that IL-6 expression persisted at incubation temperatures in the upper end of the physiological range that induced heat shock and attenuated the expression of functionally active TNF-alpha in LPS-stimulated HuMoM phi.
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Vilcek, J., V. J. Palombella, D. Henriksen-DeStefano, C. Swenson, R. Feinman, M. Hirai, and M. Tsujimoto. "Fibroblast growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors." Journal of Experimental Medicine 163, no. 3 (March 1, 1986): 632–43. http://dx.doi.org/10.1084/jem.163.3.632.
Abstract:
Tumor necrosis factor (TNF) is a monocyte-derived protein cytotoxic or cytostatic for some tumor cell lines. Here we show that highly purified E. coli-derived recombinant human TNF stimulated the growth of human FS-4 diploid fibroblasts. Stimulation of cell growth was demonstrable at a TNF concentration of 10 pg/ml (3 X 10(-13) M). Maximal stimulation was attained at TNF concentrations of 10 ng/ml (3 X 10(-10) M) or higher. Growth-stimulatory activity of TNF was inhibited by an mAb neutralizing the cytotoxic activity of TNF. Growth stimulation was not inhibited by another mAb specific for TNF, lacking neutralizing activity for the cytotoxic activity of TNF. Growth stimulation by TNF was more marked and more sustained in the presence of greater than or equal to 10% FCS than in medium with less than or equal to 5% FCS. Addition of TNF to confluent FS-4 cultures also produced a marked stimulation of cell growth in the presence of fresh FCS, while a much less marked stimulation was seen in the absence of FCS. Stimulation of confluent cultures by TNF in serum-free medium was enhanced by insulin, suggesting that insulin or insulin-like growth factor(s) in the serum can act synergistically with TNF in producing growth stimulation. While the growth-stimulatory effects of TNF and insulin were synergistic, the actions of TNF and epidermal growth factor (EGF) were less than additive, suggesting that TNF and EGF may activate identical or similar pathways. We conclude that stimulation of cell growth is probably a physiological function of TNF, and that the cytotoxic and cytostatic actions of TNF may be the result of an anomalous growth signal transduction in neoplastic cells lacking the constraints of normal growth control mechanisms.
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Slungaard, A., G. M. Vercellotti, G. Walker, R. D. Nelson, and H. S. Jacob. "Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium." Journal of Experimental Medicine 171, no. 6 (June 1, 1990): 2025–41. http://dx.doi.org/10.1084/jem.171.6.2025.
Abstract:
Eosinophils (EOs) participate in a variety of inflammatory states characterized by endothelial cell damage, such as vasculitis, pneumonitis, and endocarditis. We find that 100 U/ml TNF-alpha/cachectin (TNF), a concentration attainable in the blood of humans with parasitic infestations, stimulates highly purified populations of EOs to damage human umbilical vein endothelial cells (HUVEC), a model of human endothelium. This TNF-dependent EO cytotoxicity is strongly inhibited by heparin and methyprednisolone but unaffected by the platelet-activating factor antagonist BN52012 or scavengers of superoxide anion and H2O2, superoxide dismutase and catalase. However, addition of a physiologically relevant concentration of Br- (100 microM) enhances EO/TNF damage to HUVEC, implicating the possible participation of EO peroxidase (EPO) in the killing mechanism. EOs adherent to FCS-coated plastic wells more than double their production of superoxide anion and the cytotoxic EPO-derived oxidant HOBr when exposed to TNF, showing that TNF activates the respiratory burst of EOs attached to a "physiologic" surface. Unlike PMNs, EOs were not irreversibly activated to kill unopsonized endothelium by previous exposure to TNF, and did not degranulate or upregulate CR3 expression as detected by Mo1 in the presence of 100 U/ml TNF. HUVEC exposed 18 h to TNF were considerably more susceptible to lysis by PMA-activated EOs and reagent H2O2, demonstrating a direct effect of TNF upon endothelium, perhaps through inhibition of antioxidant defenses. These findings suggest that abnormally elevated serum levels of TNF may provoke EOs to damage endothelial cells and thereby play a role in the pathogenesis of tissue damage in hypereosinophilic states.
26
Kubota, Takeshi, Jidong Fang, Tetsuya Kushikata, and James M. Krueger. "Interleukin-13 and transforming growth factor-β1 inhibit spontaneous sleep in rabbits." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279, no. 3 (September 1, 2000): R786—R792. http://dx.doi.org/10.1152/ajpregu.2000.279.3.r786.
Abstract:
Proinflammatory cytokines, including interleukin-1β and tumor necrosis factor-α are involved in physiological sleep regulation. Interleukin (IL)-13 and transforming growth factor (TGF)-β1 are anti-inflammatory cytokines that inhibit proinflammatory cytokines by several mechanisms. Therefore, we hypothesized that IL-13 and TGF-β1 could attenuate sleep in rabbits. Three doses of IL-13 (8, 40, and 200 ng) and TGF-β1 (40, 100, and 200 ng) were injected intracerebroventricularly 3 h after the beginning of the light period. In addition, one dose of IL-13 (200 ng) and one dose of TGF-β1 (200 ng) were injected at dark onset. The two higher doses of IL-13 and the highest dose of TGF-β1 significantly inhibited spontanenous non-rapid eye movement sleep (NREMS) when they were given in the light period. IL-13 also inhibited NREMS after dark onset administration; however, the inhibitory effect was less potent than that observed after light period administration. The 40-ng dose of IL-13 inhibited REMS duration during the dark period. TGF-β1 administered at dark onset had no effect on sleep. These data provide additional evidence for the hypothesis that a brain cytokine network is involved in regulation of physiological sleep.
27
Mogulevtseva, J. A., A. V. Mezentsev, and S. A. Bruskin. "Impact of Metalloproteinase 1 Deficiency Induced by Specific Small Hairpin RNA on the Physiological Effects of Tumor Necrosis Factor." Russian Journal of Genetics 54, no. 8 (August 2018): 960–66. http://dx.doi.org/10.1134/s1022795418080094.
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Amari, T., K. Kubo, T. Kobayashi, and M. Sekiguchi. "Effects of recombinant human superoxide dismutase on tumor necrosis factor-induced lung injury in awake sheep." Journal of Applied Physiology 74, no. 6 (June 1, 1993): 2641–48. http://dx.doi.org/10.1152/jappl.1993.74.6.2641.
Abstract:
Tumor necrosis factor alpha (TNF) is a mediator of acute lung injury after endotoxemia, but the precise mechanism of TNF-induced lung injury remains unclear. To clarify the role of oxygen radicals, especially superoxide anion, in TNF-induced lung injury, we examined the effects of recombinant human superoxide dismutase (rhSOD; 4,200 U/mg) on lung physiological and biochemical changes after TNF infusion in awake sheep (n = 17). We prepared chronically instrumented sheep for lung lymph collection and hemodynamic monitoring. Recombinant human TNF (3.5 micrograms/kg iv) induced a biphasic response in awake sheep. Pulmonary hypertension peaked within 15 min of initiation of TNF and remained elevated for 3 h, followed by increased lung vascular permeability. rhSOD attenuated the pulmonary hypertension in both early and late phases but caused no change in the timing or magnitude of lung fluid balance changes during the late phase. Thromboxane A2 (thromboxane B2) and prostacyclin (6-ketoprostaglandin F1 alpha) metabolite levels in plasma and lymph increased after the TNF infusion, and rhSOD attenuated these changes. The intravenous infusion of rhSOD resulted in the appearance of significant levels of SOD activity in both plasma and lung lymph before and after TNF infusion. These findings suggest that superoxide anion may be implicated in the pathogenesis of the pulmonary hypertension induced by TNF in sheep.
29
Qin, Wen, Zhuo Yang, Jiyong Yin, Di Chen, Junsheng Huo, Jingbo Wang, Liyuan Wang, and Qin Zhuo. "Effect Assessment of Aurantio-Obtusin on Novel Human Renal Glomerular Endothelial Cells Model Using a Microfluidic Chip." Nutrients 14, no. 21 (November 2, 2022): 4615. http://dx.doi.org/10.3390/nu14214615.
Abstract:
Cassiae semen is widely used as a raw material of health food. Anthraquinone compounds, the main components in cassiae semen, have been reported to show nephrotoxicity. Aurantio-obtusin (AO) is a major anthraquinone compound extracted from cassiae semen. This study investigates the effects of AO on the morphology and physiological function of human renal glomerular endothelial cells (HRGECs) on a microfluidic chip device for the first time. HRGECs were cultured on a microfluidic plate and exposed to a series of AO concentrations. Compared with traditional 96-well culture, HRGECs cultured on the microfluidic chip appeared to better mimic the glomerular microenvironment in vivo. AO induced different degrees of damage to cellular morphology and physiological function. The leakage of lactate dehydrogenase (LDH), as well as the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and monocyte chemoattractant protein 1 (MCP-1), increased in the AO treated groups. At the same time, cell viability and expression of ZO-1 in the AO treated groups decreased in a dose-dependent manner. The innovative device enables direct visualization and quantification to evaluate the cytotoxic effects of AO on HRGECs, and provides a useful visual in vitro model for studying health effect of health food.
30
Pamir, Nathalie, Timothy S. McMillen, Karl J. Kaiyala, Michael W. Schwartz, and Renée C. LeBoeuf. "Receptors for Tumor Necrosis Factor-α Play a Protective Role against Obesity and Alter Adipose Tissue Macrophage Status." Endocrinology 150, no. 9 (May 28, 2009): 4124–34. http://dx.doi.org/10.1210/en.2009-0137.
Abstract:
Abstract TNF-α signals through two receptors, TNFR1 and TNFR2. Our goals were: 1) determine the role of TNFRs in obesity and metabolic disease and 2) investigate whether TNFRs contribute to the link between obesity and adipose tissue macrophage infiltration and polarization. R1−/−R2−/− (RKO) and wild-type (WT) mice were fed standard chow or a high-fat/high-sucrose diet (HFHS) over 14 wk. Body composition, food intake, and energy expenditure were measured. Oral glucose tolerance and insulin sensitivity tests assessed glucose homeostasis. Adipose tissue and systemic inflammatory status were evaluated by quantifying plasma adipokine levels and macrophage-specific gene expression in fat. RKO mice were heavier (10%) and fatter (18%) than WT controls at 4 wk of age and were 26% heavier and 50% fatter than WT after 14 wk of HFHS diet feeding. Age- and diet-adjusted 24-h oxygen consumption, activity, and respiratory exchange ratio were significantly reduced in RKO mice. Obese RKO mice were markedly insulin resistant, suggesting that intact TNFR signaling is not required for the effect of obesity to impair glucose metabolism. Adipose tissue from HFHS-fed RKO mice exhibited increased macrophage infiltration, but compared with WT mice, macrophage phenotypic markers featured a predominance of antiinflammatory M2 over proinflammatory M1 cells. TNFRs play a physiological role to limit body weight and adiposity by modestly increasing metabolic rate and fatty acid oxidation, and they are required for obesity-induced activation of adipose tissue macrophages. Despite these effects, TNFRs are not required for obesity-induced insulin resistance.
31
Lanuza, Guillermo M., Patricia E. Saragüeta, Ursula A. Bussmann, and J. Lino Barañao. "Paradoxical effects of tumour necrosis factor-α on rat granulosa cell DNA synthesis." Reproduction, Fertility and Development 14, no. 3 (2002): 133. http://dx.doi.org/10.1071/rd01103.
Abstract:
Tumour necrosis factor- α (TNF-α ) has been proposed as an intraovarian modulator of granulosa cell function. The effect of TNF-α on DNA synthesis in cultured rat granulosa cells was examined. Tumour necrosis factor-α stimulated thymidine incorporation when added in the presence of transforming growth factor-β (TGF-β). In contrast, the co-mitogenic effect of follicle-stimulating hormone (FSH) and TGF-β was inhibited in a dose-dependent manner by TNF-α . Inhibition of FSH-dependent DNA synthesis by TNF-α was also found when cultures were co-stimulated with activin A. The inhibitory action of TNF-α on FSH-treated cultures was not associated with changes in cell viability. The inhibitory effects of TNF-α could not be solely explained by a decrease in cAMP levels, since TNF-α was also able to inhibit the stimulation by dibutyryl-cAMP and TGF-β on granulosa cell DNA synthesis. These results suggest that TNF-α regulation of granulosa cell growth is elicited either independently or downstream from gonadotrophin-induced cAMP production. The actions of TNF-α could be only partially mimicked by a cell-permeable analogue of ceramide, thus indicating that actions of this cytokine can not be fully ascribed to an activation of sphingomyelinase. Data presented here indicate that, in addition to its previously demonstrated inhibitory effects on gonadotrophin-induced cell differentiation, TNF-α may also exert a marked inhibition on hormonally stimulated immature granulosa cell proliferation. In contrast to this inhibitory action, this cytokine could amplify the mitogenic action of putative intraovarian growth regulators such as TGF-β. These observations add further support to the notion that TNF-α plays a physiological role as a paracrine modulator of follicle development and may be also relevant to the alteration of ovarian function during physiopathological processes.
32
Short, Sarah M., Gregory A. Talbott, and Rudolph L. Juliano. "Integrin-mediated Signaling Events in Human Endothelial Cells." Molecular Biology of the Cell 9, no. 8 (August 1998): 1969–80. http://dx.doi.org/10.1091/mbc.9.8.1969.
Abstract:
Vascular endothelial cells are important in a variety of physiological and pathophysiological processes. The growth and functions of vascular endothelial cells are regulated both by soluble mitogenic and differentiation factors and by interactions with the extracellular matrix; however, relatively little is known about the role of the matrix. In the present study, we investigate whether integrin-mediated anchorage to a substratum coated with the extracellular matrix protein fibronectin regulates growth factor signaling events in human endothelial cells. We show that cell adhesion to fibronectin and growth factor stimulation trigger distinct initial tyrosine phosphorylation events in endothelial cells. Thus, integrin-dependent adhesion of endothelial cells leads to tyrosine phosphorylation of both focal adhesion kinase and paxillin, but not of several growth factor receptors. Conversely, EGF stimulation causes receptor autophosphorylation, with no effect on focal adhesion kinase or paxillin tyrosine phosphorylation. Adhesion to fibronectin, in the absence of growth factors, leads to activation of MAPK. In addition, adhesion to fibronectin also potentiates growth factor signaling to MAPK. Thus, polypeptide growth factor activation of MAPK in anchored cells is far more effective than in cells maintained in suspension. Other agonists known to activate MAPK were also examined for their ability to activate MAPK in an anchorage-dependent manner. The neuropeptide bombesin, the bioactive lipid lysophosphatidic acid (LPA), and the cytokine tumor necrosis factor α, which signal through diverse mechanisms, were all able to activate MAPK to a much greater degree in fibronectin-adherent cells than in suspended cells. In addition, tumor necrosis factor α activation of c-Jun kinase (JNK) was also much more robust in anchored cells. Together, these data suggest a cooperation between integrins and soluble mitogens in efficient propagation of signals to downstream kinases. This cooperation may contribute to anchorage dependence of mitogenic cell cycle progression.
33
Mattijssen, Sandy, and Richard J. Maraia. "LARP4 Is Regulated by Tumor Necrosis Factor Alpha in a Tristetraprolin-Dependent Manner." Molecular and Cellular Biology 36, no. 4 (December 7, 2015): 574–84. http://dx.doi.org/10.1128/mcb.00804-15.
Abstract:
LARP4 is a protein with unknown function that independently binds to poly(A) RNA, RACK1, and the poly(A)-binding protein (PABPC1). Here, we report on its regulation. We found a conserved AU-rich element (ARE) in the human LARP4 mRNA 3′ untranslated region (UTR). This ARE, but not its antisense version or a point-mutated version, significantly decreased the stability of β-globin reporter mRNA. We found that overexpression of tristetraprolin (TTP), but not its RNA binding mutant or the other ARE-binding proteins tested, decreased cellular LARP4 levels. RNA coimmunoprecipitation showed that TTP specifically associated with LARP4 mRNAin vivo. Consistent with this, mouse LARP4 accumulated to higher levels in TTP gene knockout (KO) cells than in control cells. Stimulation of WT cells with tumor necrosis factor alpha (TNF-α), which rapidly induces TTP, robustly decreased LARP4 with a coincident time course but had no such effect on LARP4B or La protein or on LARP4 in the TTP KO cells. The TNF-α-induced TTP pulse was followed by a transient decrease in LARP4 mRNA that was quickly followed by a subsequent transient decrease in LARP4 protein. Involvement of LARP4 as a target of TNF-α–TTP regulation provides a clue as to how its functional activity may be used in a physiologic pathway.
34
Izvolskaia, Marina, Viktoria Sharova, and Liudmila Zakharova. "Prenatal Programming of Neuroendocrine System Development by Lipopolysaccharide: Long-Term Effects." International Journal of Molecular Sciences 19, no. 11 (November 21, 2018): 3695. http://dx.doi.org/10.3390/ijms19113695.
Abstract:
Various stress factors during critical periods of fetal development modulate the epigenetic mechanisms controlling specific genes, which can affect the structure and function of physiological systems. Maternal immune stress by bacterial infection simulated by lipopolysaccharide (LPS) in an experiment is considered to be a powerful programming factor of fetal development. Studies of the molecular mechanisms controlling the formation and functioning of physiological systems are in the pilot stage. LPSs are the most potent natural inflammation factors. LPS-induced increases in fetal levels of pro- and anti-inflammatory cytokines can affect brain development and have long-term effects on behavior and neuroendocrine functions. The degradation of serotonergic neurons induced by LPS in the fetus is attributed to the increased levels of interleukin (IL)-6 and tumor necrosis factor (TNFα) as well as to anxiety and depression in children. Dopamine deficiency causes dysthymia, learning disability, and Parkinson’s disease. According to our data, an LPS-induced increase in the levels of IL-6, leukemia inhibitory factor (LIF), and monocyte chemotactic protein (MCP-1) in maternal and fetal rats during early pregnancy disturbs the development and functioning of gonadotropin-releasing hormone production and reproductive systems. It is important to note the high responsiveness of epigenetic developmental mechanisms to many regulatory factors, which offers opportunities to correct the defects.
35
Mikhaylova, Irina V., Tiina Kuulasmaa, Jarmo Jääskeläinen, and Raimo Voutilainen. "Tumor Necrosis Factor-α Regulates Steroidogenesis, Apoptosis, and Cell Viability in the Human Adrenocortical Cell Line NCI-H295R." Endocrinology 148, no. 1 (January 1, 2007): 386–92. http://dx.doi.org/10.1210/en.2006-0726.
Abstract:
TNF-α regulates the hypothalamo-pituitary-adrenal axis at several levels. It has been shown to modify adrenal steroidogenesis in many species, and it is supposed to act as an auto/paracrine factor. However, its significance in human adrenocortical function remains unclear. Therefore, we investigated the effect of TNF-α on adrenal steroidogenesis, expression of the key steroidogenic genes, apoptosis, and cell viability in the human adrenocortical cell line NCI-H295R. TNF-α treatment (1 nm for 48 h) decreased the basal production of cortisol, androstenedione, dehydroepiandrosterone sulfate (DHEAS), and aldosterone (14, 18, 35, and 52%, respectively), and the 8-bromo-cAMP-induced production of cortisol, androstenedione, dehydroepiandrosterone (DHEA), and DHEAS (44, 66, 58, and 48%, respectively). However, when the steroid production data were normalized by the cell number, TNF-α increased the basal production of cortisol, androstenedione, DHEA, DHEAS, and aldosterone (137, 121, 165, 73, and 28%, respectively), and the 8-bromo-cAMP-induced production of cortisol, DHEAS, and aldosterone (122, 121, and 256%, respectively). This was accompanied by a parallel increase in the expression of the genes encoding for the steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase 2, and 17-hydroxylase/17,20-lyase (74, 200, and 50%, respectively; quantitative real-time RT-PCR analysis). TNF-α increased caspase 3/7 activity (an indicator of apoptosis) and decreased cell viability dose and time dependently. The effect of TNF-α on apoptosis was neutralized by a monoclonal TNF-α antibody. These findings indicate that TNF-α is a potent regulator of steroidogenesis and cell viability in adrenocortical cells. TNF-α may have physiological and/or pathophysiological significance as an endocrine and/or paracrine/autocrine regulator of adrenocortical function.
36
Tannenbaum, C. S., J. A. Major, and T. A. Hamilton. "IFN-gamma and lipopolysaccharide differentially modulate expression of tumor necrosis factor receptor mRNA in murine peritoneal macrophages." Journal of Immunology 151, no. 12 (December 15, 1993): 6833–39. http://dx.doi.org/10.4049/jimmunol.151.12.6833.
Abstract:
Abstract Expression of TNF receptor (TNFR) mRNA has been examined in murine peritoneal macrophages stimulated with LPS and/or IFN-gamma. LPS markedly enhanced expression of a heterogenous population of mRNA, which hybridized with a cDNA encoding the type II TNFR. mRNA expression was optimally induced by 4 to 8 h and returned to baseline by 24 h after stimulation. Interestingly, though IFN-gamma can synergize with LPS for the expression of TNF-alpha, it abrogated the LPS-mediated enhancement of type II TNFR in a dose-dependent fashion. IFN-alpha, though less effective, had a qualitatively comparable effect. These effects were selective for the type II TNFR because levels of mRNA encoding the type I TNFR did not vary appreciably with any of the treatments described. The effects of IFN-gamma on LPS-mediated TNFR expression were dependent on the sequence of exposure; pretreatment with IFN-gamma was most effective at blocking response to LPS, whereas IFN-gamma added 1 h after initiation of LPS treatment had little or no effect. The effects of both LPS and IFN-gamma on type II TNFR expression were mediated at least in part by modulation of transcription. The effects of both LPS and IFN-gamma were also independent of protein synthesis because inclusion of cycloheximide in the treatment protocol did not abrogate either the inductive or the suppressive effects. These findings suggest that IFN-gamma and LPS modulate the physiologic action of TNF through complex mechanisms involving effects on the transcription of TNF-alpha itself and on receptors through which it may act in autocrine or paracrine fashion.
37
Halim, Sobia Ahsan, Almas Gul Sikandari, Ajmal Khan, Abdul Wadood, Muhammad Qaiser Fatmi, René Csuk, and Ahmed Al-Harrasi. "Structure-Based Virtual Screening of Tumor Necrosis Factor-α Inhibitors by Cheminformatics Approaches and Bio-Molecular Simulation." Biomolecules 11, no. 2 (February 22, 2021): 329. http://dx.doi.org/10.3390/biom11020329.
Abstract:
Tumor necrosis factor-α (TNF-α) is a drug target in rheumatoid arthritis and several other auto-immune disorders. TNF-α binds with TNF receptors (TNFR), located on the surface of several immunological cells to exert its effect. Hence, the use of inhibitors that can hinder the complex formation of TNF-α/TNFR can be of medicinal significance. In this study, multiple chem-informatics approaches, including descriptor-based screening, 2D-similarity searching, and pharmacophore modelling were applied to screen new TNF-α inhibitors. Subsequently, multiple-docking protocols were used, and four-fold post-docking results were analyzed by consensus approach. After structure-based virtual screening, seventeen compounds were mutually ranked in top-ranked position by all the docking programs. Those identified hits target TNF-α dimer and effectively block TNF-α/TNFR interface. The predicted pharmacokinetics and physiological properties of the selected hits revealed that, out of seventeen, seven compounds (4, 5, 10, 11, 13–15) possessed excellent ADMET profile. These seven compounds plus three more molecules (7, 8 and 9) were chosen for molecular dynamics simulation studies to probe into ligand-induced structural and dynamic behavior of TNF-α, followed by ligand-TNF-α binding free energy calculation using MM-PBSA. The MM-PBSA calculations revealed that compounds 4, 5, 7 and 9 possess highest affinity for TNF-α; 8, 11, 13–15 exhibited moderate affinities, while compound 10 showed weaker binding affinity with TNF-α. This study provides valuable insights to design more potent and selective inhibitors of TNF-α, that will help to treat inflammatory disorders.
38
KUMAR, SUNIL, DOLKER LAMO, GEETA GAHLAWAT, VIJAY K. BHARTI, and KRISHNA KUMAR. "Effect of endurance load exercise on physio-biochemical and hormonal parameters of single-humped camels (Camelus dromedarius) at high altitude." Indian Journal of Animal Sciences 92, no. 7 (June 19, 2022): 837–42. http://dx.doi.org/10.56093/ijans.v92i7.115253.
Abstract:
The present study was carried out for 7 days on four adult low-lander single-humped camels to know the effectof endurance load exercise on physiological, biochemical, hormonal, and inflammatory cytokines at high altitude.A significant 1.5 to 3 fold increase was observed in physiological responses, viz. the respiration and heart rate onthe 1st and 7th day after the load endurance exercise. Further, serum triglycerides levels were significantly increased on the 7th day after the load endurance exercise, whereas other biochemical parameters were unaffected. However, hormones and inflammatory cytokines responses, viz. cortisol, cardiac-troponin (C-troponin), interleukin-6 (IL-6), tri-iodothyronine (T3), thyroxine, thyroid-stimulating hormone (TSH), and tumor necrosis factor-α (TNF-α) were significantly increased on 1st and 7th day after the endurance exercise. These physio-biochemical changes during load endurance exercise indicated that low-lander single-humped camels have low endurance and are under physiological stress in high altitude conditions. Thus, the present study has brought new primary data and information on physiobiochemical parameters of the single-humped camel at high altitude. This data may help identify suitable camels for load-carrying and other logistics at high altitude areas
39
Denzler, Karen, Jessica Moore, Heather Harrington, Kira Morrill, Trung Huynh, Bertram Jacobs, Robert Waters, and Jeffrey Langland. "Characterization of the Physiological Response followingIn VivoAdministration ofAstragalus membranaceus." Evidence-Based Complementary and Alternative Medicine 2016 (2016): 1–13. http://dx.doi.org/10.1155/2016/6861078.
Abstract:
The botanical,Astragalus membranaceus, is a therapeutic in traditional Chinese medicine. Limited literature exists on the overallin vivoeffects ofA. membranaceuson the human body. This study evaluates the physiological responses toA. membranaceusby measuring leukocyte, platelet, and cytokine responses as well as body temperature and blood pressure in healthy individuals after thein vivoadministration ofA. membranaceus. A dose-dependent increase in monocytes, neutrophils, and lymphocytes was measured 8–12 hours after administration and an increase in the number of circulating platelets was seen as early as 4 hours. A dynamic change in the levels of circulating cytokines was observed, especially in interferon-γand tumor necrosis factor-α, IL-13, IL-6, and soluble IL-2R. Subjective symptoms reported by participants were similar to those typically experienced in viral type immune responses and included fatigue, malaise, and headache. Systolic and diastolic blood pressure were reduced within 4 hours after administration, while body temperature mildly increased within 8 hours after administration. In general, all responses returned to baseline values by 24 hours. Collectively, these results support the role ofA. membranaceusin priming for a potential immune response as well as its effect on blood flow and wound healing.
40
Gao, Jing, Dongsheng Wang, Dan Liu, Min Liu, Yehua Ge, Minghong Jiang, Yanxin Liu, and Dexian Zheng. "Tumor necrosis factor–related apoptosis-inducing ligand induces the expression of proinflammatory cytokines in macrophages and re-educates tumor-associated macrophages to an antitumor phenotype." Molecular Biology of the Cell 26, no. 18 (September 15, 2015): 3178–89. http://dx.doi.org/10.1091/mbc.e15-04-0209.
Abstract:
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy, because it can induce apoptosis in various tumor cells but not in most normal cells. Although it is well known that TRAIL and its receptors are expressed in many types of normal cells, including immune cells, their immunological effects and regulatory mechanisms are still obscure. In the present study, we demonstrated that TRAIL affected the activity of NF-κB (nuclear factor-κB) and the expression of its downstream proinflammatory cytokines IL-1β (interleukin-1β), IL-6, and tumor necrosis factor α in macrophages. TRAIL also induced microRNA-146a (miR-146a) expression in an NF-κB–dependent manner. As a result, miR-146a was involved as a negative-feedback regulator in the down-regulation of proinflammatory cytokine expression. In addition, the suppression of histone deacetylase (HDAC) activities by trichostatin A improved miR-146a expression due to the up-regulation of the DNA-binding activity of NF-κB at the miR-146a promoter in TRAIL-induced macrophages, suggesting that histone acetylation was involved in the suppression of miR-146a expression. Further investigation revealed that the HDAC subtype HDAC1 directly regulated the expression of miR-146a in TRAIL-stimulated macrophages. Finally, the TRAIL-sensitive human non small cell lung carcinoma cell line NCI-H460 was used to elucidate the physiological significance of TRAIL with respect to tumor-associated macrophages (TAMs). We demonstrated that TRAIL re-educated TAMs to an M1-like phenotype and induced cytotoxic effects in the tumor cells. These data provide new evidence for TRAIL in the immune regulation of macrophages and may shed light on TRAIL-based antitumor therapy in human patients.
41
Abe, Shogo, Misako Ueno, Mami Nishitani, Tetsuya Akamatsu, Takumi Sato, Marie Shimoda, Hiroki Kanaoka, Yoshitaka Nii, Hiroko Yamasaki, and Keizo Yuasa. "Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway." Biomolecules 10, no. 10 (October 21, 2020): 1468. http://dx.doi.org/10.3390/biom10101468.
Abstract:
Citrus sudachi is a well-known fruit in Tokushima Prefecture, Japan, and its peels are rich in phytochemicals, including phenolic compounds. Although it is expected that the extract of the C. sudachi peel elicits various beneficial physiological activities, the effect on the skin has not been investigated. In this study, we report that the aqueous extract from the peel of C. sudachi suppresses cell proliferation of the immortalized human keratinocyte cell line, HaCaT, and primary normal human epidermal keratinocytes. The extract of C. sudachi peel suppressed epidermal growth factor (EGF)-induced EGF receptor activation and tumor necrosis factor (TNF)-α-induced extracellular regulated kinase (ERK) 1/2 activation, which suggests that the extract exerts its inhibitory effect through inhibition of both the EGF receptor (EGFR) and its downstream molecules. Additionally, the extract of C. sudachi peel potentiated calcium-induced keratinocyte differentiation. These results suggest that the extract of C. sudachi peel may have beneficial effects against skin diseases that are characterized by hyperproliferation of epidermal keratinocytes, such as those seen in psoriasis and in cutaneous squamous cell carcinoma.
42
Mygind, Leda, Marianne Skov-Skov Bergh, Vivien Tejsi, Ramanan Vaitheeswaran, Kate L. Lambertsen, Bente Finsen, and Athanasios Metaxas. "Tumor Necrosis Factor (TNF) Is Required for Spatial Learning and Memory in Male Mice under Physiological, but Not Immune-Challenged Conditions." Cells 10, no. 3 (March 9, 2021): 608. http://dx.doi.org/10.3390/cells10030608.
Abstract:
Increasing evidence demonstrates that inflammatory cytokines—such as tumor necrosis factor (TNF)—are produced at low levels in the brain under physiological conditions and may be crucial for synaptic plasticity, neurogenesis, learning and memory. Here, we examined the effects of developmental TNF deletion on spatial learning and memory using 11–13-month-old TNF knockout (KO) and C57BL6/J wild-type (WT) mice. The animals were tested in the Barnes maze (BM) arena under baseline conditions and 48 h following an injection of the endotoxin lipopolysaccharide (LPS), which was administered at a dose of 0.5 mg/kg. Vehicle-treated KO mice were impaired compared to WT mice during the acquisition and memory-probing phases of the BM test. No behavioral differences were observed between WT and TNF-KO mice after LPS treatment. Moreover, there were no differences in the hippocampal content of glutamate and noradrenaline between groups. The effects of TNF deletion on spatial learning and memory were observed in male, but not female mice, which were not different compared to WT mice under baseline conditions. These results indicate that TNF is required for spatial learning and memory in male mice under physiological, non-inflammatory conditions, however not following the administration of LPS. Inflammatory signalling can thereby modulate spatial cognition in male subjects, highlighting the importance of sex- and probably age-stratified analysis when examining the role of TNF in the brain.
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Mitlianga, P., G. Germanidis, H. M. Moutsopoulos, and G. K. Papadopoulos. "The Effect of Transforming Growth Factor β1, and Tumor Necrosis Factor α on the Cytotoxic-Cytostatic Action of Interleukin-1 (α and β Isoforms) on the Pancreatic B Cell Line Rin-5ah." International Journal of Immunopathology and Pharmacology 8, no. 2 (May 1995): 67–77. http://dx.doi.org/10.1177/039463209500800201.
Abstract:
The rat pancreatic β cell line RIN-5AH was treated with the cytokines IL-1 (α and β), TNFα and TGF-β1, in order to examine at the clonal level the reported mostly cytotoxic effects of IL-1, on isolated islets of Langerhans and islet cell preparations. In contrast to what has been previously reported for whole islets and islet cell preparations we find that IL-1 (α or β) is not cytotoxic to the RIN-5AH cells in logarithmic growth phase to any extent, even at very high cytokine concentrations (125 nM). Furthermore, TNFα does not in any way potentiate IL-1 cytotoxicity. Transforming growth factor-β1 (TGF-β1) at concentrations of 80 pM to 2 nM, has a potentiating effect on IL-1 cytotoxicity (conc. 5 nM) for this clonal cell line. The effect is proportional to the level of TGF-β1 present and is exerted regardless of the IL-1 isoform used. The effects of the various cytokines, alone or in combination, were only observed at high (25 mM) glucose concentrations, and no such effects were observed at the physiological (5 mM) glucose concentration. Furthermore the combination of TGF-β1 and IL-1 inhibits the release of insulin by these cells, whereas either cytokine alone has no effect. We conclude that the RIN-5AH cells in showing little cytotoxic/cytostatic response to IL-1 are responding more as isolated β cells than as cells within islets. The potentiation of the action of IL-1 by TGF-β1 on these cells is a matter of further investigation.
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Velayudhan, Silpa Mullakkalparambil, Kerstin Brügemann, Shahin Alam, Tong Yin, Chinnasamy Devaraj, Veerasamy Sejian, Eva Schlecht, and Sven König. "Molecular, Physiological and Hematological Responses of Crossbred Dairy Cattle in a Tropical Savanna Climate." Biology 12, no. 1 (December 23, 2022): 26. http://dx.doi.org/10.3390/biology12010026.
Abstract:
A comprehensive study was conducted to assess the effects of seasonal transition and temperature humidity index (THI) on the adaptive responses in crossbred dairy cows reared in a tropical savanna region. A total of 40 lactating dairy cattle reared by small-scale dairy farmers in Bengaluru, India, were selected for this study. The research period comprised the transitioning season of summer to monsoon, wherein all traits were recorded at two points, one representing late summer (June) and the other early monsoon (July). A set of extensive variables representing physiological responses (pulse rate, respiration rate, rectal temperature, skin surface temperature), hematological responses (hematological profile), production (test day milk yield, milk composition) and molecular patterns (PBMC mRNA relative expression of selective stress response genes) were assessed. A significant effect of seasonal transition was identified on respiration rate (RR), skin surface temperature, mean platelet volume (MPV), platelet distribution width (PDWc), test day milk yield and on milk composition variables (milk density, lactose, solids-not-fat (SNF) and salts). The THI had a significant effect on RR, skin surface temperature, platelet count (PLT), plateletcrit (PCT) and PDWc. Lastly, THI and/or seasonal transition significantly affected the relative PBMC mRNA expression of heat shock protein 70 (HSP70), interferon beta (IFNβ), IFNγ, tumor necrosis factor alpha (TNFα), growth hormone (GH) and insulin-like growth factor-1 (IGF-1) genes. The results from this study reveal environmental sensitivity of novel physiological traits and gene expressions to climatic stressors, highlighting their potential as THI-independent heat stress biomarkers.
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Hill, Molly R., Stephen Clarke, Kerry Rodgers, Brandi Thornhill, Jeffrey M. Peters, Frank J. Gonzalez, and Jeffrey M. Gimble. "Effect of Peroxisome Proliferator-Activated Receptor Alpha Activators on Tumor Necrosis Factor Expression in Mice during Endotoxemia." Infection and Immunity 67, no. 7 (July 1, 1999): 3488–93. http://dx.doi.org/10.1128/iai.67.7.3488-3493.1999.
Abstract:
ABSTRACT Inflammatory mediators orchestrate the host immune and metabolic response to acute bacterial infections and mediate the events leading to septic shock. Tumor necrosis factor (TNF) has long been identified as one of the proximal mediators of endotoxin action. Recent studies have implicated peroxisome proliferator-activated receptor alpha (PPARα) as a potential target to modulate regulation of the immune response. Since PPARα activators, which are hypolipidemic drugs, are being prescribed for a significant population of older patients, it is important to determine the impact of these drugs on the host response to acute inflammation. Therefore, we examined the role of PPARα activators on the regulation of TNF expression in a mouse model of endotoxemia. CD-1 mice treated with dietary fenofibrate or Wy-14,643 had fivefold-higher lipopolysaccharide (LPS)-induced TNF plasma levels than LPS-treated control-fed animals. Higher LPS-induced TNF levels in drug-fed animals were reflected physiologically in significantly lower glucose levels in plasma and a significantly lower 50% lethal dose than those in LPS-treated control-fed animals. Utilizing PPARα wild-type (WT) and knockout (KO) mice, we showed that the effect of fenofibrate on LPS-induced TNF expression was indeed mediated by PPARα. PPARα WT mice fed fenofibrate also had a fivefold increase in LPS-induced TNF levels in plasma compared to control-fed animals. However, LPS-induced TNF levels were significantly decreased and glucose levels in plasma were significantly increased in PPARα KO mice fed fenofibrate compared to those in control-fed animals. Data from peritoneal macrophage studies indicate that Wy-14,643 modestly decreased TNF expression in vitro. Similarly, overexpression of PPARα in 293T cells decreased activity of a human TNF promoter-luciferase construct. The results from these studies suggest that any anti-inflammatory activity of PPARα in vivo can be masked by other systemic effects of PPARα activators.
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Thomson, B. M., G. R. Mundy, and T. J. Chambers. "Tumor necrosis factors alpha and beta induce osteoblastic cells to stimulate osteoclastic bone resorption." Journal of Immunology 138, no. 3 (February 1, 1987): 775–79. http://dx.doi.org/10.4049/jimmunol.138.3.775.
Abstract:
Abstract Antigen- or mitogen-stimulated leukocytes release bone-resorbing activity into culture supernatants in vitro. Among the agents likely to be present in such supernatants are monocyte-derived tumor necrosis factor (TNF-alpha) and lymphocyte-derived tumor necrosis factor (TNF-beta) (lymphotoxin), both of which have recently been shown to stimulate bone resorption in organ culture. To identify the mechanism of action of these agents, we compared bone resorption by isolated osteoclasts with bone resorption by osteoclasts cocultured with osteoblastic cells, and with bone resorption by osteoclasts incubated with supernatants from osteoblastic cells, in the presence and absence of recombinant TNF-alpha and TNF-beta. We found that neither TNF-alpha nor TNF-beta had any significant effect on bone resorption by isolated osteoclasts, but in the presence of osteoblasts the agents caused a twofold to threefold stimulation of bone resorption. A similar degree of stimulation was achieved by supernatants from osteoblasts incubated with TNF before addition to osteoclasts, compared with supernatants to which TNF were added after osteoblast incubation. These experiments suggest that TNF-alpha and TNF-beta stimulate bone resorption through a primary effect on osteoblastic cells, which are induced by TNF to produce a factor that stimulates osteoclastic resorption. Half-maximal stimulation of resorption occurred at 1.5 X 10(-10) M and 2.5 X 10(-10) M for TNF-alpha and TNF-beta, respectively. This degree of potency is comparable to that of parathyroid hormone, the major physiologic systemic regulator of bone resorption, and suggests that the TNF may exert a significant influence on osteoclastic bone resorption in vivo.
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Chen, Yi-Jian, Li-Qun Zhang, Guang-Ping Wang, Hui Zeng, Ben Lü, Xu-Liang Shen, Zhi-Ping Jiang, and Fang-Ping Chen. "Adiponectin inhibits tissue factor expression and enhances tissue factor pathway inhibitor expression in human endothelial cells." Thrombosis and Haemostasis 100, no. 08 (2008): 291–300. http://dx.doi.org/10.1160/th08-02-0124.
Abstract:
SummaryTissue factor (TF) plays a pivotal role in thrombus formation and atherogenesis in acute coronary syndrome. Tissue factor pathway inhibitor (TFPI) is a specific physiological inhibitor of TF/ FVIIa complex that regulates TF-induced coagulation. Adiponectin (Adp) is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Adp inhibits inflammatory cytokine and adhesion molecules expression, and it can prevent endothelial dysfunction. In this study, we investigated the effects of Adp on tumor necrosis factor-α (TNF-α)-induced expression of TF and TFPI in human umbilical vein endothelial cells (HU-VECs), and the signaling transduction pathways involved. It was found that Adp significantly inhibited both TF protein expression and activity in TNF-α-stimulated HUVECs. In the meanwhile, it increased TFPI protein expression and activity for about two folds. Adp also inhibited TF mRNA expression induced by TNF-α, but had no effect on TFPI mRNA expression. The inhibitory effect of Adp onTNF-α-inducedTF expression was prevented by pretreatment with Rp-cAMPs, a PKA inhibitor. Adp increased intracellular cAMP content and PKA activity levels in a dose-dependent manner. Phosphorylation of IκB-α was decreased by Adp, but phosphorylation of p44/42MAPK, SAPK/ JNK, and p38MAPK were not affected. These results suggested that Adp inhibits TF expression through inhibition of a PKA dependent nuclear factor- κB (NF-κB) signaling pathway. It was also found that adiponectin promoted Akt and AMP-activated protein kinase phosphorylation. The inhibitory effect of Adp on TNF-α-induced TF synthesis was abrogated in part by pretreatment with the PI3kinase inhibitor LY 294002, suggesting that Akt activation might inhibit TF expression induced by TNF-α. The inhibitory effect of Adp is almost completely abrogated by inhibition of both the cAMP/PKA pathway and PI3K/Akt pathway. In conclusion, our data indicated that inhibition of NF-κB through stabilization of IκB-α and activation of Akt phosphorylation may mediate the inhibitory effect of Adp on TF expression; but the enhancement effect of Adp on the TFPI production might occur via translational rather than transcriptional regulation.
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Bauldry, S. A., C. E. McCall, S. L. Cousart, and D. A. Bass. "Tumor necrosis factor-alpha priming of phospholipase A2 activation in human neutrophils. An alternative mechanism of priming." Journal of Immunology 146, no. 4 (February 15, 1991): 1277–85. http://dx.doi.org/10.4049/jimmunol.146.4.1277.
Abstract:
Abstract The cytokine, TNF-alpha, interacts with human neutrophils (PMN) via specific membrane receptors and primes leukotriene B4 (LTB4) production in PMN for subsequent stimulation by calcium ionophores. We have further examined the effects of TNF-alpha on arachidonic acid (AA) release, LTB4 production, and platelet-activating factor (PAF) formation in PMN by prelabeling cells with either [3H]AA or [3H]lyso-PAF, priming with human rTNF-alpha, and then stimulating with the chemotactic peptide, FMLP. TNF-alpha, alone, had little effect; minimal AA release, LTB4 or PAF production occurred after PMN were incubated with 0 to 1000 U/ml TNF-alpha. However, when PMN were first preincubated with 100 U/ml TNF-alpha for 30 min and subsequently challenged with 1 microM FMLP, both [3H] AA release and LTB4 production were elevated two- to threefold over control values. Measurement of AA mass by gas chromatography and LTB4 production by RIA confirmed the radiolabeled results. TNF-alpha priming also increased PAF formation after FMLP stimulation. These results demonstrate that TNF-alpha priming before stimulation with a physiologic agonist can enhance activation of phospholipase A2 (PLA2) resulting in increased AA release and can facilitate the activities of 5-lipoxygenase (LTB4 production) and acetyltransferase (PAF formation). Reports in the literature have hypothesized that the priming mechanism involves either production of PLA2 metabolites, increased diglyceride (DG) levels, or enhanced cytosolic calcium levels induced by the priming agent. We investigated these possibilities in TNF-alpha priming of PMN and report that TNF-alpha had no direct effect on PLA2 activation or metabolite formation. Treatment of PMN with TNF-alpha did not induce DG formation and, in the absence of cytochalasin B, no increased DG production (measured by both radiolabel techniques and mass determinations) occurred after TNF-alpha priming followed by FMLP stimulation. TNF-alpha also had no effect on basal cytosolic calcium and did not enhance intracellular calcium levels after FMLP stimulation. These results suggest that an alternative, as yet undefined, mechanism is active in TNF-alpha priming of human PMN.
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Delfraissy, J. F., C. Wallon, F. Boue, F. Barresinoussi, and P. Galanaud. "Tumor necrosis factor-alpha inhibits the competence signal delivered by HIV to normal B cells." Journal of Immunology 146, no. 5 (March 1, 1991): 1516–21. http://dx.doi.org/10.4049/jimmunol.146.5.1516.
Abstract:
Abstract Polyclonal B cell activation is commonly observed in HIV-infected patients. The coordinate delivery of a number of signals is required for B cell response. This work was designed to better define the role of HIV in the first steps of normal human B cells activation. We show that the infectious virus or recombinant envelope proteins can render B cells responsive to the growth-promoting effect of several T cell-derived IL, IL-2, IL-4, and low m.w. (12-kDa) BCGF. HIV acts in the absence of monocytes and on different populations of B cells. The competence signal can be provided by recombinant gp160 envelope protein. CD4 molecule is not involved in the interaction of HIV with B cells. In addition, we demonstrate that tumor necrosis factor alpha has no promoting activity when B cells are preactivated by HIV and it can suppress the response of HIV-preactivated B cells to IL-2, IL-4, and 12-kDa BCGF. Thus, the HIV envelope can deliver an early signal to normal B cells and modulate B cell response to physiologic signals. The possible relevance of this phenomenon to the immune defect observed in HIV patients is discussed.
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Chung, Yi, Yi-Ting Hsiao, and Wen-Ching Huang. "Physiological and Psychological Effects of Treadmill Overtraining Implementation." Biology 10, no. 6 (June 10, 2021): 515. http://dx.doi.org/10.3390/biology10060515.
Abstract:
Overtraining in athletes usually causes profound and lasting deleterious effects on the maintenance of health and exercise capacity. Here, we established an overtraining animal model to investigate the physiological modulation for future strategic applications in vivo. We subjected C57BL/6 mice to exhaustive treadmill exercises daily for 8 weeks (the exhaustive exercise group). Next, the physiological and psychological outcomes were compared with the regular exercise and sedentary groups. Outcome measures included growth, glucose tolerance, exercise metabolism profiles, cytokine levels, intestinal tight junction gene expression, and psychological behavioral changes. Our results revealed that overtraining negatively affected the physiological and psychological changes in the current model. The exhaustive exercise group exhibited significantly lower endurance performance and imbalanced energy expenditure, causing a decrease in body fat mass and slowing down the growth curve. In addition, the inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) and immune cells (neutrophils and monocytes) were significantly elevated after successive exhaustive exercise interventions. Furthermore, overtraining-induced stress resulted in increased anxiety status and decreased food intake. Our findings reinforce the idea that an imbalance between exercise and recovery can impair health and performance maintenance after overtraining. This study highlights the maladaptation of overtraining and provides an animal model to determine the effectiveness of possible strategies, including nutrition and monitoring, for treatment and prevention of overtraining syndromes in future studies.