Expression of IL-10 receptors on epithelial cells from the murine small and large intestine

The appearance of chronic intestinal inflammation in IL-10 knockout mice su ggests IL-10 may inhibit adverse responses to luminal antigen, Moreover, th is inflammation is associated with an increase in class II MHC molecule exp ression on intestinal epithelial cells, Thus, the role of IL-10 regulation in epithelial cell function was investigated, Using RT-PCR, it was shown th at intestinal epithelial cells express mRNA for both subunits of the IL-10 receptor-signaling complex, In addition, biotinylated IL-10 was shown to bi nd to both cultured and freshly isolated intestinal epithelial cells prepar ed from the small or large intestine, This binding appeared specific as it was blocked by neutralizing antibodies to IL-10 but not the isotype control . Moreover, an excess of native IL-10 also inhibited the binding of radiola beled IL-10, To evaluate whether IL-10 mediated any functions through this receptor, epithelial cells were cultured with IL-10 alone or with IFN-gamma plus IL-10, IL-10 alone had no detectable effects on epithelial cell growt h or their expression of class II MHC molecules but it did antagonize the e ffect of IFN-gamma on the viability of cultured cells. In addition, IL-10 b locked the IFN-gamma-induced expression of class II MHC molecules on cultur ed epithelial cells. These results suggest that IL-10 binds to a specific r eceptor on intestinal epithelial cells and may regulate the contribution of epithelial cells to the inflammatory and immune response in the digestive tract.