Expression of IL-10 receptors on epithelial cells from the murine small and large intestine
Expression of IL-10 receptors on epithelial cells from the murine small and large intestine
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DOI：
10.1093/intimm/12.2.133
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发表时间：
2000-02-01
影响因子：
4.4
通讯作者：
Ernst, PB
中科院分区：
文献类型：
--
作者：
Denning, TL;Campbell, NA;Ernst, PB
IL-10基因敲除小鼠出现慢性肠道炎症，提示IL-10可能抑制对管腔抗原的不良反应，而且这种炎症与肠上皮细胞上II类MHC分子表达的增加有关。因此，我们研究了IL-10对上皮细胞功能的调节作用。显示肠上皮细胞表达IL-10受体-信号传导复合物的两种亚基的mRNA。此外，显示生物素化的IL-10结合培养的和新鲜分离的从小肠或大肠制备的肠上皮细胞，这种结合似乎是特异性的，因为它被IL-10的中和抗体阻断，而不是同种型对照。此外，过量的天然IL-10也抑制放射性标记的IL-10的结合。为了评价IL-10是否通过该受体介导任何功能，将上皮细胞与单独的IL-10或与IFN-γ加IL-10一起培养，单独的IL-10对上皮细胞生长或其II类MHC分子的表达没有可检测的作用，但它确实拮抗IFN-γ的作用。γ对培养细胞的活力的影响。此外，IL-10阻断了IFN-γ诱导的培养上皮细胞上II类MHC分子的表达。这些结果表明，IL-10结合到肠上皮细胞上的特异性受体，并可能调节上皮细胞对消化道炎症和免疫反应的贡献。
The appearance of chronic intestinal inflammation in IL-10 knockout mice suggests IL-10 may inhibit adverse responses to luminal antigen, Moreover, this inflammation is associated with an increase in class II MHC molecule expression on intestinal epithelial cells, Thus, the role of IL-10 regulation in epithelial cell function was investigated, Using RT-PCR, it was shown that intestinal epithelial cells express mRNA for both subunits of the IL-10 receptor-signaling complex, In addition, biotinylated IL-10 was shown to bind to both cultured and freshly isolated intestinal epithelial cells prepared 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 radiolabeled 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 growth or their expression of class II MHC molecules but it did antagonize the effect of IFN-gamma on the viability of cultured cells. In addition, IL-10 blocked the IFN-gamma-induced expression of class II MHC molecules on cultured epithelial cells. These results suggest that IL-10 binds to a specific receptor on intestinal epithelial cells and may regulate the contribution of epithelial cells to the inflammatory and immune response in the digestive tract.