Production of matrix metalloproteinase-9 in CaCO-2 cells in response to inflammatory stimuli

J Interferon Cytokine Res. 2001 Feb;21(2):93-8. doi: 10.1089/107999001750069953.


Matrix metalloproteinase-9 (MMP-9) may play an important role in the development of inflammatory bowel disease (IBD). However, the cellular source of MMP-9 in the inflamed mucosa of IBD remains unclear. Here we report that MMP-9 mRNA is expressed in CaCO-2 cells, an intestinal epithelial cell line, and that its expression is upregulated by inflammatory stimuli. Stimulation of CaCO-2 cells with interleukin-1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha) led to a dose-dependent increase in expression and secretion of MMP-9. In contrast, bacterial lipopolysaccharide (LPS) failed to induce expression or secretion of MMP-9, suggesting that an inflammatory reaction leading to cytokine release is a necessary step for the induction of MMP-9 release in intestinal epithelial cells. Additional studies show that induction of MMP-9 mRNA peaked at 16 h of IL-1beta stimulation, whereas expression of monocyte chemoattractant protein-1 (MCP-1) and IL-8 both peaked at 3 h of stimulation. Treatment of CaCO-2 cells with rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, significantly reduced secretion of MMP-9, indicating that agents that activate PPAR-gamma may have therapeutic use in patients with IBD.

MeSH terms

  • Caco-2 Cells
  • Humans
  • Inflammation Mediators / pharmacology
  • Inflammatory Bowel Diseases / enzymology*
  • Inflammatory Bowel Diseases / etiology*
  • Inflammatory Bowel Diseases / genetics
  • Interleukin-1 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Rosiglitazone
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / agonists
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / drug effects


  • Inflammation Mediators
  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Rosiglitazone
  • Matrix Metalloproteinase 9