IL-1beta is known promote cyclooxygenase-2 (COX- 2) and matrix metalloproteinase-2 (MMP-2) expression. This study focuses on the characterization of the signaling cascade associated with IL-1beta-induced matrix metalloproteinase-2 (MMP- 2) regulation in human chondrocytes. The decrease in collagen levels in the conditioned media was prevented by a broad spectrum MMP inhibitor, suggesting that IL-1beta promotes the proteolytic process leading to MMP-2 activation. IL-1beta-related MMP-2 expression was found to be dependent on prostaglandin E2 (PGE2) production. In addition, the induction of COX-2 and MMP-2 was inhibited by the pretreatment of chondrocytes with a SB203580 or Ro 31-8220, indicating the involvement of protein kinase C (PKC) or p38 mitogen-activated protein kinase (MAPK). However, there is no cross-talk between PKC and p38 MAPK in the IL-1beta-induced MMP-2 activation. Taken together, these results demonstrated that IL-1beta induces MMP-2 expression through the PGE2-dependent mechanism in human chondrocytes.
Chondrocytes/drug effects/*enzymology/metabolism ; Dinoprostone/analysis/*metabolism ; Gelatinase A/analysis/*biosynthesis ; Humans ; Indoles/pharmacology ; Interleukin-1/*pharmacology ; Isoenzymes/antagonists & inhibitors/metabolism ; Nitrobenzenes/pharmacology ; Phosphorylation/drug effects ; Prostaglandin-Endoperoxide Synthase/metabolism ; Protein Kinase C/antagonists & inhibitors/metabolism ; Research Support, Non-U.S. Gov't ; Sulfonamides/pharmacology ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases/metabolism