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• W1996208529 endingPage "R118" @default.
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• W1996208529 abstract "IntroductionTumor necrosis factor-alpha (TNFα) plays a pivotal role in rheumatoid arthritis (RA); however, the mechanism of action of TNFα antagonists in RA is poorly defined. Immunization of DBA/1 mice with glucose-6-phosphate isomerase (GPI) induces severe acute arthritis. This arthritis can be controlled by TNFα antagonists, suggesting similar etiology to RA. In this study, we explored TNFα-related mechanisms of arthritis.MethodsFirst, we performed GeneChip analysis using splenocytes of mice with GPI-induced arthritis. Expression of TNFα-induced adipose-related protein (TIARP) mRNA and protein in spleens, joints and lymph nodes was evaluated, and fluctuation of TIARP mRNA was analyzed after administration of anti-TNFα monoclonal antibody (mAb). Localization of TIARP in spleen and joints was also explored. Six-transmembrane epithelial antigen of the prostate (STEAP) families of proteins, the human ortholog of TIARP gene, were also evaluated in human peripheral blood mononucleocytes and synovium.ResultsAmong the arrayed TNFα-related genes, the expression of TIARP mRNA was the highest (more than 20 times the control). TIARP mRNA was detected specifically in joints and spleens of arthritic mice, and their levels in the synovia correlated with severity of joint swelling. Treatment with anti-TNF mAb significantly reduced TIARP mRNA expression in splenocytes. Among the splenocytes, CD11b+ cells were the main source of TIARP mRNA. Immunohistochemistry showed that TIARP protein was mainly localized in hyperplastic synovium. Among the STEAP family of proteins, STEAP4 was highly upregulated in joints of patients with RA and especially co-localized with CD68+ macrophages.ConclusionsThe results shed light on the new mechanism of action of TNFα antagonists in autoimmune arthritis, suggesting that TIARP plays an important role in inflammatory arthritis, through the regulation of inflammatory cytokines." @default.
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• W1996208529 date "2009-01-01" @default.
• W1996208529 modified "2023-10-08" @default.
• W1996208529 title "Tumor necrosis factor α-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis" @default.
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• W1996208529 doi "https://doi.org/10.1186/ar2779" @default.
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