{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:56:48Z","timestamp":1784915808369,"version":"3.55.0"},"reference-count":38,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,10,1]]},"abstract":"<jats:p>It has been suggested that Fas-mediated apoptosis plays an important role in the pathogenesis of autoimmune thyroid diseases. Our previous studies have demonstrated that normal primary thyroid epithelial cells are resistant to Fas-mediated apoptosis, but the resistance can be overcome by pretreatment with a combination of interferon-\u03b3 (IFN-\u03b3) and IL-1\u03b2. To understand the molecular mechanism responsible for the IFN-\u03b3\/IL-1\u03b2 effects, we profiled changes in the transcription induced by these two cytokines in normal human thyroid cells, using cDNA microarrays. We found that IFN-\u03b3\/IL-1\u03b2 showed a significant increase in apoptosis-related genes such as inducible nitric oxide synthase (iNOS), receptor-interacting protein 2 (RIP2), and caspases 10. These increases were confirmed by other methods, including real-time PCR and Western blot. Furthermore, the sensitization of primary thyroid epithelial cells to Fas-mediated apoptosis by IFN-\u03b3\/IL-1\u03b2 was significantly blocked by a general caspase inhibitor, z-VAD, or by the combination of two specific individual caspase inhibitors. In addition, our results showed that IFN-\u03b3\/IL-1\u03b2 enhance p38 MAPK phosphorylation and that SB 203580, a p38 MAPK inhibitor, can inhibit IFN-\u03b3\/IL-1\u03b2-induced p38 MAPK phosphorylation. SB 203580 also significantly prevented cytokine-induced iNOS expression and caspase activation and thus blocked Fas-mediated apoptosis of thyroid cells sensitized by IFN-\u03b3\/IL-1\u03b2. In conclusion, our data suggest that both p38 MAPK and iNOS are involved in IFN-\u03b3\/IL-1\u03b2-induced sensitization of the thyroid cells to Fas-mediated apoptosis via the activation of caspases 3, 7, and 10 and that this pathway may be further activated by BID. This hints that inflammatory cytokines regulate death-receptor-mediated apoptosis at multiple points in the process.<\/jats:p>","DOI":"10.1210\/en.2007-0126","type":"journal-article","created":{"date-parts":[[2007,7,20]],"date-time":"2007-07-20T00:44:26Z","timestamp":1184892266000},"page":"4844-4852","source":"Crossref","is-referenced-by-count":24,"title":["Microarray Analysis of Cytokine Activation of Apoptosis Pathways in the Thyroid"],"prefix":"10.1210","volume":"148","author":[{"given":"Su He","family":"Wang","sequence":"first","affiliation":[{"name":"Departments of Internal Medicine (S.H.W., M.V.A., Y.Y.F., J.R.B.), Medical School, University of Michigan Medical Center, Ann Arbor, Michigan 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Van Antwerp","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (S.H.W., M.V.A., Y.Y.F., J.R.B.), Medical School, University of Michigan Medical Center, Ann Arbor, Michigan 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