Matiilvsin is a member of the matrix rnetalloproteinase Miperfarnily (MMPsl that participate in tissue remodeling under physiological and pathological con ditiuii. Although Tiiatriiysin (MM P 7) has a broad substrate specificity, it is primarily secreted towards the lumen by glandular epithelia. These obser\ations. together with data localizing MMP 7 to defense Paneth cells in the munnc small intestine, suggest that it may function in host defense mecha nisrns. We are studying the effect of the interaction between bacterial adhesins and In i in an epithelial cells on the expression, regulation, and activity of M.M.P 7. We have tound that the infection of colon, bladder, and lung epithelial cells with FimH-engineered E. coli bacteria markedly increases MMP 7 mRNA levels. By Western blotting, we have detected both the latent and the active forms of MMP 7 in the conditioned media. The increase in the secretion of MMP 7 is lapid, depends on t he number of bacterial cells present in t he initial inoculum, and requires de nova protein synthesis. Furthermore, the induction of MMP 7 is specifically inhibited by rnannose, indicating that the binding of the bacteria to mannosylated receptors is essential to trigger the response in the epithelial cells. In contrast, bacteria did not induce MMP 7 expression in fibroblasts -or keratiiiocytes, and the expression of other MMPs was not affected by the baiteria. These studies indicate a novel and potentially important function of MMP 7 in a primary host defense mechanism in epithelial cells.
|State||Published - Dec 1 1997|