Inhibitory effect of cyclo-oxygenase-2 inhibitor on the production of matrix metalloproteinases in rheumatoid fibroblast-like synoviocytes.
Cyclo-oxygenase (COX)-2 has been associated with inflammation in rheumatoid arthritis (RA), but its role in joint destruction remains unclear. In this study, we investigated the effect on cultured rheumatoid fibroblast-like synoviocytes (FLS) of the selective COX-2 inhibitor celecoxib on the expression of matrix metalloproteinases (MMPs), which play an important role in tissue degradation and angiogenesis in rheumatoid synovium. Treatment with nontoxic doses of celecoxib resulted in dose-dependent inhibition of MMP-1, -2, and -3 secretion from FLS when measured by enzyme-linked immunosorbent assay. Celecoxib suppressed proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta) induced augmentation of the gelatinolytic activity on zymography. These results suggest that COX-2 inhibitors might influence matrix degradation or angiogenesis in RA by downregulating the expression of various MMPs in rheumatoid FLS.
Cha
H S
HS
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135-710, Korea. chahs@samsung.co.kr
Ahn
K S
KS
Jeon
C H
CH
Kim
J
J
Koh
E M
EM
D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D000068579:Celecoxib; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology*; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D020782:Matrix Metalloproteinases; D000068579:Celecoxib