Regulation mechanism of production and secretion of mucin in intestinal goblet cells

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Intestinal mucin is a large molecular glycoprotein produced mainly in goblet cells, and important to protect the epithelial surface from harmful pathogens. We studied on effect of some cytokines on regulation mechanism of mucin expression in the human colon cancer cell lines, LS174T and HT29. IL-13 stimulated mucin secretion from LS174T cells. RT-PCR showed that LS174T and HT29 cells expressed mRNA of receptors of IL-4, IL-13 and TNF-α. IL-4, IL-13 and TNF-α stimulated the mRNA expression of MUC2, which is a major mucin core protein in the colon, in LS174T cells. IL-4 and IL-13, however, did not stimulate MUC2 gene expression in HT29 cells. TNF-a stimulated MUC2 gene expression in HT29 cells. IL-4 and IL-13 activated phosphorylation of STAT6 in the JAK/STAT signal transduction pathway in both cell lines. IL-4 and IL-13 but not TNF-α activated phosphorylation of MAPK in LS174T cells, whereas IL-4, IL-13 and TNF-α activated phosphorylation of MAPK in HT29 cells. A specific inhibitor of MAPK kinase, U0126, inhibited the MUC2 gene expression induced with IL-4 and IL-13 in LS174T cells and the expression induced with TNF-α in HT29. These results suggest that MUC2 gene expression is stimulated with IL-4, IL-13, or TNF-α through a MAPK pathway in the human colon cancer cell lines.