TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages

Circ J. 2004 Apr;68(4):396-9. doi: 10.1253/circj.68.396.

Abstract

The expression of TWEAK (TNFSF12) and TweakR/Fn14 was detected in regions rich in macrophage/foam cells in atherosclerotic plaques. The role of TWEAK in monocytes in relation to atherogenesis was investigated by analyzing the cellular events induced by TWEAK in a human macrophage-like cell line, THP-1. TWEAK induced various molecular mediators of atherogenesis, such as IL-6, MCP-1, IL-8 and MMP-9, and the induction was augmented by interferon-gamma. TWEAK-induced activation of MMP-9 was mediated by activation of NF-kappaB. These results suggest that TWEAK is involved in atherosclerosis by inducing pro-inflammatory cytokines and extracellular matrix degrading enzymes, which reduce plaque stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins
  • Carotid Stenosis / etiology
  • Carotid Stenosis / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology
  • Carrier Proteins / physiology*
  • Cell Line / metabolism
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / genetics
  • Cytokine TWEAK
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Enzyme Induction / drug effects
  • Foam Cells / metabolism
  • Gene Expression Profiling
  • Humans
  • I-kappa B Proteins / metabolism
  • Interferon-gamma / pharmacology*
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Proline / analogs & derivatives*
  • Proline / pharmacology
  • Recombinant Proteins / pharmacology
  • Thiocarbamates / pharmacology
  • Transcriptional Activation / drug effects
  • Tumor Necrosis Factors

Substances

  • Apoptosis Regulatory Proteins
  • CCL2 protein, human
  • Carrier Proteins
  • Chemokine CCL2
  • Cytokine TWEAK
  • Cytokines
  • I-kappa B Proteins
  • Interleukins
  • NF-kappa B
  • Recombinant Proteins
  • TNFSF12 protein, human
  • Thiocarbamates
  • Tumor Necrosis Factors
  • prolinedithiocarbamate
  • Interferon-gamma
  • Proline
  • Matrix Metalloproteinase 9