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Published Online: 7 July 2004

Production of Matrix Metalloproteinase-9 in CaCO-2 Cells in Response to Inflammatory Stimuli

Publication: Journal of Interferon & Cytokine Research
Volume 21, Issue Number 2

Abstract

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-1β (IL-1β) or tumor necrosis factor-α (TNF-α) 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-1β 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-γ (PPAR-γ) agonist, significantly reduced secretion of MMP-9, indicating that agents that activate PPAR-γ may have therapeutic use in patients with IBD.

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cover image Journal of Interferon & Cytokine Research
Journal of Interferon & Cytokine Research
Volume 21Issue Number 2February 2001
Pages: 93 - 98
PubMed: 11244573

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Published online: 7 July 2004
Published in print: February 2001

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Xiaodong Gan
Department of Lipid Biochemistry, Merck Research Laboratories, Rahway, NJ 07065.
Birming Wong
Department of Lipid Biochemistry, Merck Research Laboratories, Rahway, NJ 07065.
Samuel D. Wright
Department of Lipid Biochemistry, Merck Research Laboratories, Rahway, NJ 07065.
Tian-Quan Cai
Department of Lipid Biochemistry, Merck Research Laboratories, Rahway, NJ 07065.

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