{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:17:53Z","timestamp":1761488273613},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T00:00:00Z","timestamp":1246233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the molecular mechanisms of CCL13\/monocyte chemoattractant protein 4 (MCP\u20104) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using RNase protection assays and enzyme\u2010linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2\/MCP\u20101 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The interleukin\u20106 (IL\u20106)\u2013type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL\u20106 nor tumor necrosis factor \u03b1 could stimulate the expression of CCL13 in synovial fibroblasts; IL\u20101\u03b2 was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT\u20105, ERK\u20101\/2, and p38 as critical factors involved in OSM\u2010dependent transcription and messenger RNA stabilization of CCL13.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In contrast to other prominent cytokines involved in the pathogenesis of RA, OSM can strongly up\u2010regulate the expression of CCL13, a chemokine recently identified in the synovial fluid of patients with RA. Despite potent OSM\u2010induced signal transduction in all types of fibroblasts analyzed, only synovial fibroblasts secreted CCL13, which might be indicative of tissue\u2010specific imprinting of different fibroblasts during development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24602","type":"journal-article","created":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T15:05:41Z","timestamp":1246287941000},"page":"1932-1943","source":"Crossref","is-referenced-by-count":37,"title":["Induction of CCL13 expression in synovial fibroblasts highlights a significant role of oncostatin M in rheumatoid 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