Celecoxib inhibits production of MMP and NO via down-regulation of NF-kappa B and JNK in a PGE2 independent manner in human articular chondrocytes

作者：Tsutsumi R; Ito H^*; Hiramitsu T; Nishitani K; Akiyoshi M; Kitaori T; Yasuda T; Nakamura T

来源：Rheumatology International, 2008, 28(8): 727-736.

DOI：10.1007/s00296-007-0511-6

• COX-2 inhibitor
• MMP-1
• MMP-3
• nitric oxide
• human articular chondrocyte

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-kappa B (NF-kappa B) 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-1 beta-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 mu M but not 100 nM of celecoxib. The inhibitors of NF-kappa B, JNK and p38, but not ERK, decreased IL-1 beta-enhanced MMP-1, MMP-3 and NO production, respectively, and 100 nM celecoxib down-regulated the phosphorylation of NF-kappa B 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-kappa B and JNK MAPK.

• 出版日期2008-6