{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T02:27:38Z","timestamp":1761964058455},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,3,4]],"date-time":"2005-03-04T00:00:00Z","timestamp":1109894400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The cytochrome P450 enzyme CYP7B catalyzes the conversion of dehydroepiandrosterone (DHEA) into 7\u03b1\u2010hydroxy\u2010DHEA (7\u03b1\u2010OH\u2010DHEA). This metabolite can stimulate the immune response. We previously reported that the severity of murine collagen\u2010induced arthritis is correlated with CYP7B messenger RNA (mRNA) expression and activity in the arthritic joint. The purpose of this study was to investigate the presence of 7\u03b1\u2010OH\u2010DHEA in synovial samples and the cytokine regulation of CYP7B activity in fibroblast\u2010like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The presence of 7\u03b1\u2010OH\u2010DHEA was examined in synovial biopsy tissues, synovial fluid, and serum by radioimmunoassay. The effect of cytokines on CYP7B mRNA expression and CYP7B activity in FLS was examined by determining the formation of the CYP7B enzyme product 7\u03b1\u2010OH\u2010DHEA with the use of high\u2010performance liquid chromatography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CYP7B enzyme product 7\u03b1\u2010OH\u2010DHEA was found in synovial biopsy tissues, synovial fluid, and serum from RA patients. The proinflammatory cytokines tumor necrosis factor \u03b1 (TNF\u03b1), interleukin\u20101\u03b1 (IL\u20101\u03b1), IL\u20101\u03b2, and IL\u201017 up\u2010regulated CYP7B activity in an FLS cell line 2\u201310\u2010fold. Enhanced CYP7B activity was correlated with an increase in CYP7B mRNA. The cytokine transforming growth factor \u03b2 inhibited CYP7B activity. Moreover, CYP7B activity was detected in 10 of 13 unstimulated synovial fibroblast cell lines. Stimulation with TNF\u03b1 increased CYP7B activity in all cell lines tested.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exposure to the proinflammatory cytokines TNF\u03b1, IL\u20101\u03b1, IL\u20101\u03b2, and IL\u201017 increases CYP7B activity in synovial tissue. Increased CYP7B activity leads to higher levels of the DHEA metabolite 7\u03b1\u2010OH\u2010DHEA in synovial fluid, which may contribute to the maintenance of the chronic inflammation observed in RA patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20950","type":"journal-article","created":{"date-parts":[[2005,3,4]],"date-time":"2005-03-04T15:53:16Z","timestamp":1109951596000},"page":"770-778","source":"Crossref","is-referenced-by-count":49,"title":["CYP7B expression and activity in fibroblast\u2010like synoviocytes from patients with rheumatoid arthritis: Regulation by proinflammatory cytokines"],"prefix":"10.1002","volume":"52","author":[{"given":"John","family":"Dulos","sequence":"first","affiliation":[]},{"given":"Monique A. 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