Cyclooxygenase inhibitors augment the production of pro-matrix metalloproteinase 9 (progelatinase B) in rabbit articular chondrocytes.
Matrix metalloproteinase 9 (MMP-9/gelatinase B) has recently been proposed to participate in the destruction of articular cartilage. Here, we report that interleukin 1 (IL-1) enhances the production of the precursor of MMP-9 in rabbit articular chondrocytes in primary culture, and this IL-1-mediated production of proMMP-9 is greatly augmented by cyclooxygenase inhibitors such as diclofenac and indomethacin, whereas the constitutive production of proMMP-2 (progelatinase A) is not modulated by IL-1 and/or cyclooxygenase inhibitors. Exogenous prostaglandin (PG) E1 and PGE2 suppress the proMMP-9 production in a dose-dependent manner. Similar results are also obtained with cultured rabbit synoviocytes. These results provide the first evidence that PGE down-regulates the production of proMMP-9 in chondrocytes and synoviocytes. Thus, cyclooxygenase inhibitors probably exert undesirable catabolic actions on the maintenance of articular cartilage under inflammatory conditions.
Ito
A
A
Department of Biochemistry, Tokyo College of Pharmacy, Japan.
Nose
T
T
Takahashi
S
S
Mori
Y
Y
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis* / Q000378:metabolism; D004008:Diclofenac / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004792:Enzyme Precursors / Q000096:biosynthesis*; D018093:Gelatinases / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D011817:Rabbits; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D004792:Enzyme Precursors; D004008:Diclofenac; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020780:Matrix Metalloproteinase 9; D000527:Alprostadil; D015232:Dinoprostone; D007213:Indomethacin