MUC2
mucin is a secretory
glycoprotein which is produced from the intestinal goblet cells and is a major component of the intestinal epithelial mucus. The biological function of MUC2
mucin is considered to be the protection of intestinal epithelial surface, whereas the regulatory mechanism of MUC2
mucin production in immune response is not completely understood. We have studied the effects of
cytokines,
IL-4,
IL-13 and
TNF-alpha, on the regulation of MUC2
mRNA in the human
colonic cancer cell lines, LS174T and HT29. The quantitative reverse transcription-polymerase chain reaction showed that single addition of
IL-4,
IL-13 and
TNF-alpha to cell culture induced about two-fold increase of MUC2
mRNA level in LS174T cells.
Interleukin-4 and
IL-13 activated phosphorylation of
mitogen-activated protein kinase in LS174T cells. A specific inhibitor of
mitogen-activated protein kinase pathway,
U0126, totally inhibited the increase of MUC2
mRNA by
IL-4 or
IL-13 in those cells. Therefore,
mitogen-activated
protein activation of
kinase is required for the increase of MUC2
mRNA by
IL-4 or
IL-13 in LS174T cells. In contrast to LS174T cells, only
TNF-alpha increased MUC2
mRNA through a
mitogen-activated protein kinase pathway in HT29 cells that express low levels of MUC2
mRNA. These findings sustain a novel phenomenon that MUC2
mRNA expression is differently controlled by
IL-4,
IL-13, or
TNF-alpha in LS174T and HT29 cells, whereas the
mitogen-activated protein kinase pathway plays a role in the MUC2
mRNA expression induced by those
cytokines in both cell lines.