IL-1beta-induced expression of matrix metalloproteinases and gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) in a chondrosarcoma cell line (OUMS-27)

Rheumatol Int. 2001 Oct;21(2):45-52. doi: 10.1007/s002960100129.

Abstract

The purpose of this study was to examine how chondrocytes are involved in the molecular mechanism of inflammation in rheumatoid arthritis (RA). A chondrosarcoma cell line (OUMS-27) was cultured and treated with interleukin-1beta (IL-1beta). Changes in the expression levels of matrix metalloproteinase-1 (MMP-1), metalloproteinase-13 (MMP-13), and gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) were assessed by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays. IL-1beta induced the expressions of MMP-1, MMP-13, and GLS mRNAs and proteins in a dose-dependent manner. Selective inhibition of the p38 mitogen-activated protein kinase (p38 MAPK) pathway with SB 203580 and SB 202190 blocked the expression of MMP-1, MMP-13, and GLS more strongly than selective in hibition of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway by PD 98059. These findings suggest that chondrocytes may intensify cartilage destruction and inflammation in RA by the induction of MMP-1, MMP-13, and GLS by IL-1beta and that the p38 MAPK pathway plays an important role in these inductions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chondrosarcoma / pathology
  • Chondrosarcoma / physiopathology
  • Collagenases / drug effects
  • Collagenases / genetics*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression / physiology
  • Humans
  • Interleukin-1 / metabolism*
  • Interleukin-1 / pharmacology
  • Matrix Metalloproteinase 1 / drug effects
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 13
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • RNA, Messenger / analysis
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Thymidine Phosphorylase / drug effects
  • Thymidine Phosphorylase / genetics*
  • Thymidine Phosphorylase / metabolism
  • Tumor Cells, Cultured
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Interleukin-1
  • RNA, Messenger
  • Thymidine Phosphorylase
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 1