Cyclooxygenase inhibitors augment the production of pro‐matrix metalloproteinase 9 (progelatinase B) in rabbit articular chondrocytes

FEBS Letters

Mori, Yo²  Takahashi, Shuya¹  Nose, Takashi²  Ito, Akira² 

[1] Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Yoshino-Cho, Ohmiya, Saitama 330, Japan;Department of Biochemistry, Tokyo College of Pharmacy, 1432 Horinouchi, Hachioji, Tokyo 192-03, Japan

关键词: Matrix metalloproteinase 9;    Gelatinase B;    Cyclooxygenase inhibitor;    Prostaglandin E;    Indomethacin;    Diclofenac;    Rabbit chondrocyte;    MMP;    matrix metalloproteinase;    DMEM;    Dulbecco's modified Eagle's medium;    LAH;    lactalbumin hydrolysate;    FBS;    fetal bovine serum;    TPA;    12-O-tetradecanoylphorbol 13-acetate;    rhIL-1;    recombinant human interleukin 1;    SDS-PAGE;    sodium dodecyl sulfate-polyacrylamide gel electrophoresis;    PG;    prostaglandin;   

DOI  :  10.1016/0014-5793(95)00085-N

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown