{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:24:24Z","timestamp":1791267864824,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Th17 cells are critically involved in autoimmune disease induction and severity. Recently, we showed that Th17 cells from patients with rheumatoid arthritis (RA) directly induced a proinflammatory loop upon interaction with RA synovial fibroblasts (RASF), including increased autocrine IL-17A production. To unravel the mechanism driving this IL-17A production, we obtained primary CD4+CD45RO+CCR6+ (Th17) cells and CD4+CD45RO+CCR6\u2212 (CCR6\u2212) T cells from RA patients or healthy individuals and cocultured these with RASF. IL-1\u03b2, IL-6, IL-23p19, and cyclooxygenase (COX)-2 expression and PGE2 production in Th17\u2013RASF cultures were higher than in CCR6\u2212 T cell\u2013RASF cultures. Cytokine neutralization showed that IL-1\u03b2 and IL-6, but not IL-23, contributed to autocrine IL-17A induction. Importantly, treatment with celecoxib, a COX-2 inhibitor, resulted in significantly lower PGE2 and IL-17A, but not IFN-\u03b3, production. Combined celecoxib and TNF-\u03b1 blockade more effectively suppressed the proinflammatory loop than did single treatment, as shown by lower IL-6, IL-8, matrix metalloproteinase-1 and matrix metalloproteinase-3 production. These findings show a critical role for the COX-2\/PGE2 pathway in driving Th17-mediated synovial inflammation in an IL-23\u2013 and monocyte-independent manner. Therefore, it would be important to control PGE2 in chronic inflammation in RA and potentially other Th17-mediated autoimmune disorders.<\/jats:p>","DOI":"10.4049\/jimmunol.1300274","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T04:41:43Z","timestamp":1372740103000},"page":"1364-1372","source":"Crossref","is-referenced-by-count":98,"title":["Synovial Fibroblasts Directly Induce Th17 Pathogenicity via the Cyclooxygenase\/Prostaglandin E2 Pathway, Independent of IL-23"],"prefix":"10.1093","volume":"191","author":[{"given":"Sandra M J","family":"Paulissen","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]},{"name":"Department of Immunology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Piet","family":"van Hamburg","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]},{"name":"Department of Immunology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Davelaar","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]},{"name":"Department of Immunology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S","family":"Asmawidjaja","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]},{"name":"Department of Immunology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M W","family":"Hazes","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Lubberts","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]},{"name":"Department of Immunology, Erasmus University Medical Center, Erasmus University , 3000 DR Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,1]]},"reference":[{"key":"2025032405135999900_r1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1084\/jem.194.4.519","article-title":"Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense","volume":"194","author":"Ye","year":"2001","journal-title":"J. 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Immunol."},{"key":"2025032405135999900_r40","doi-asserted-by":"crossref","first-page":"12233","DOI":"10.1073\/pnas.0915112107","article-title":"Dual roles of PGE2-EP4 signaling in mouse experimental autoimmune encephalomyelitis","volume":"107","author":"Esaki","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032405135999900_r41","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1002\/eji.200838969","article-title":"Prostaglandin E2 enhances Th17 responses via modulation of IL-17 and IFN-\u03b3 production by memory CD4+ T cells","volume":"39","author":"Napolitani","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"2025032405135999900_r42","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1182\/blood-2008-05-155408","article-title":"Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion","volume":"112","author":"Chizzolini","year":"2008","journal-title":"Blood"},{"key":"2025032405135999900_r43","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1002\/art.24329","article-title":"GATA-3 protects against severe joint inflammation and bone erosion and reduces differentiation of Th17 cells during experimental arthritis","volume":"60","author":"van Hamburg","year":"2009","journal-title":"Arthritis Rheum."},{"key":"2025032405135999900_r44","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1002\/eji.200737840","article-title":"Enforced expression of GATA3 allows differentiation of IL-17-producing cells, but constrains Th17-mediated pathology","volume":"38","author":"van Hamburg","year":"2008","journal-title":"Eur. J. 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