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

Exp Mol Med. 2004 Jun 30;36(3):226-32. doi: 10.1038/emm.2004.31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chondrocytes / drug effects
  • Chondrocytes / enzymology*
  • Chondrocytes / metabolism
  • Cyclooxygenase 2
  • Dinoprostone / analysis
  • Dinoprostone / metabolism*
  • Humans
  • Indoles / pharmacology
  • Interleukin-1 / pharmacology*
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Membrane Proteins
  • Nitrobenzenes / pharmacology
  • Phosphorylation / drug effects
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Sulfonamides / pharmacology
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Indoles
  • Interleukin-1
  • Isoenzymes
  • Membrane Proteins
  • Nitrobenzenes
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Protein Kinase C
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 2
  • Dinoprostone
  • Ro 31-8220