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

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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.