Exp Mol Med.  2004 Jun;36(3):226-232.

Interleukin-1beta stimulates matrix metalloproteinase-2 expression via a prostaglandin E2-dependent mechanism in human chondrocytes

• Choi YA
• Lee DJ
• Lim HK
• Jeong JH
• Sonn JK
• Kang SS
• Baek SH

Abstract

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.

Keyword

chondrocytes; gelatinase A; interleukin-1; mitogen-activated; prostaglandin endoperoxide synthase; prostaglandin E; protein kinases

MeSH Terms

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