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  • Title: Celecoxib inhibits production of MMP and NO via down-regulation of NF-kappaB and JNK in a PGE2 independent manner in human articular chondrocytes.
    Author: Tsutsumi R, Ito H, Hiramitsu T, Nishitani K, Akiyoshi M, Kitaori T, Yasuda T, Nakamura T.
    Journal: Rheumatol Int; 2008 Jun; 28(8):727-36. PubMed ID: 18080123.
    Abstract:
    The purpose of this study was to examine the effects of celecoxib on matrix metalloproteinases (MMP-1 and MMP-3), nitric oxide (NO), and the phosphorylation of nuclear factor-kappaB (NF-kappaB) and three mitogen-activated protein kinases (MAPKs), (p38, JNK and ERK) in human articular chondrocytes from normal, osteoarthritis, and rheumatoid arthritis cartilages. Celecoxib at 100 nM reduced the IL-1beta-induced productions of MMP-1, MMP-3, iNOS, and NO, whereas indomethacin at 100 nM showed no effect. The additional stimulation of prostaglandin E2 (PGE2) failed to restore those productions, while the production of PGE2 were reduced by 1 and 10 microM but not 100 nM of celecoxib. The inhibitors of NF-kappaB, JNK and p38, but not ERK, decreased IL-1beta-enhanced MMP-1, MMP-3 and NO production, respectively, and 100 nM celecoxib down-regulated the phosphorylation of NF-kappaB and JNK but has no effect on either p38 or ERK. Celecoxib has inhibitory effects on MMP-1, MMP-3 and NO productions, suggesting the protective roles directly on articular chondrocytes. Despite the COX-2 selectivity, celecoxib affects those productions via not PGE2 but NF-kappaB and JNK MAPK.
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