Matrix metaloproteinase‐9 (MMP‐9) modulates mucin: Implication for the role of MMP‐9 in the pathogenesis of colitis

Mucin and intestinal trefoil factor‐3 (ITF‐3) constitute important first line defense of the intestinal epithelium. We have recently shown that epithelial derived MMP‐9 is a key mediator of tissue damage during colitis. In this study, we examined the effect of MMP‐9 on mucin, MUC‐2 and ITF‐3 expression. The effect of MMP‐9 overexpression on ITF‐3, MUC‐2 and mucin were tested using the goblet cell line, HT29‐16E and MMP‐9 knock out mice. 6–8 week old FVB/NJ wild‐type and MMP‐9 knockout mice were exposed to oral Salmonella typhimuriu (S.T.). Colonization of liver and spleen by Salmonella, weight loss and mortality were used as indicators of (S.T.)sepsis. Overexpression of MMP‐9 in HT29‐16E cells resulted in a phenotypic change in mucin, from acidic to basic mucin as well as a decrease in mucin granules as seen by electron microscopy. In addition, MMP‐9 overexpression resulted in downregulation of MUC‐2 and ITF‐3, a bactericidal protein. Further, MMP‐9 overexpression increased (S.T.) adhesion to HT29‐16E cells. In contrast, MMP‐9 knock out mice showed upregulation of goblet cells, increased acidic mucin as well as MUC‐2 and ITF‐3 expression. Importantly, MMP‐9 knock out mice were resistant to bacterial invasion and sepsis induced by (S.T.). We conclude that MMP‐9 upregulation during colitis may reduce intestinal defense mechanism, causing the colon to be susceptible to infection/inflammation