{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:11:54Z","timestamp":1791425514383,"version":"4.3.3"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2003,12,1]],"date-time":"2003-12-01T00:00:00Z","timestamp":1070236800000},"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":[[2003,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We examined the regulation of matrix metalloproteinase (MMP) production by mitogen-activated protein kinases and cyclooxygenases (COXs) in fibroblast-like synoviocytes (FLSCs). IL-1\u03b2 and TNF-\u03b1 stimulated FLSC extracellular signal-regulated kinase (ERK) activation as well as MMP-1 and -13 release. Pharmacologic inhibitors of ERK inhibited MMP-1, but not MMP-13 expression. Whereas millimolar salicylates inhibited both ERK and MMP-1, nonsalicylate COX and selective COX-2 inhibitors enhanced stimulated MMP-1 release. Addition of exogenous PGE1 or PGE2 inhibited MMP-1, reversed the effects of COX inhibitors, and inhibited ERK activation, suggesting that COX-2 activity tonically inhibits MMP-1 production via ERK inhibition by E PGs. Exposure of FLSCs to nonselective COX and selective COX-2 inhibitors in the absence of stimulation resulted in up-regulation of MMP-1 expression in an ERK-dependent manner. Moreover, COX inhibition sufficient to reduce PGE levels increased ERK activity. Our data indicate that: 1) ERK activation mediates MMP-1 but not MMP-13 release from FLSCs, 2) COX-2-derived E PGs inhibit MMP-1 release from FLSCs via inhibition of ERK, and 3) COX inhibitors, by attenuating PGE inhibition of ERK, enhance the release of MMP-1 by FLSC.<\/jats:p>","DOI":"10.4049\/jimmunol.171.11.6080","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:32:01Z","timestamp":1398029521000},"page":"6080-6089","source":"Crossref","is-referenced-by-count":57,"title":["Cyclooxygenase-2-Derived E Prostaglandins Down-Regulate Matrix Metalloproteinase-1 Expression in Fibroblast-Like Synoviocytes via Inhibition of Extracellular Signal-Regulated Kinase Activation"],"prefix":"10.1093","volume":"171","author":[{"given":"Michael H","family":"Pillinger","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"},{"name":"Hospital for Joint Diseases , New York, NY 10003"},{"name":"New York Harbor Healthcare System of the Veterans Administration , New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela B","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"},{"name":"Hospital for Joint Diseases , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia N","family":"Tolani","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"},{"name":"New York Harbor Healthcare System of the Veterans Administration , New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Apsel","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"},{"name":"Hospital for Joint Diseases , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Dinsell","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"},{"name":"Hospital for Joint Diseases , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"},{"name":"Hospital for Joint Diseases , New York, NY 10003"},{"name":"New York Harbor Healthcare System of the Veterans Administration , New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin S L","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F","family":"Gomez","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"},{"name":"Hospital for Joint Diseases , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B","family":"Abramson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"},{"name":"Hospital for Joint Diseases , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,12,1]]},"reference":[{"key":"2026020211063581800_R1","first-page":"355","volume-title":"Rheum. 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