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肠道共生菌对肠上皮中癌胚抗原相关细胞黏附分子表达的调控

Regulation by gut commensal bacteria of carcinoembryonic antigen-related cell adhesion molecule expression in the intestinal epithelium.

作者信息

Kitamura Yasuaki, Murata Yoji, Park Jung-Ha, Kotani Takenori, Imada Shinya, Saito Yasuyuki, Okazawa Hideki, Azuma Takeshi, Matozaki Takashi

机构信息

Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

出版信息

Genes Cells. 2015 Jul;20(7):578-89. doi: 10.1111/gtc.12247. Epub 2015 Apr 23.

Abstract

Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 1 and CEACAM20, immunoglobulin superfamily members, are predominantly expressed in intestinal epithelial cells (IECs) and co-localized at the apical surface of these cells. We here showed that the expression of mouse CEACAM1 and CEACAM20 at both mRNA and protein levels was markedly reduced in IECs of the small intestine by the treatment of mice with antibiotics against Gram-positive bacteria. The expression of both proteins was also decreased in IECs of the small intestine from germ-free mice, compared with that from control specific-pathogen-free mice. Exposure of intestinal organoids to IFN-γ markedly increased the expression of either CEACAM1 or CEACAM20, whereas the exposure to TNF-α increased the expression of the former protein, but not that of the latter. In contrast, the expression of CEACAM20, but not of CEACAM1, in intestinal organoids was markedly increased by exposure to butyrate, a short-chain fatty acid produced by bacterial fermentation in the intestine. Collectively, our results suggest that Gram-positive bacteria promote the mRNA expression of CEACAM1 or CEACAM20 in the small intestine. Inflammatory cytokines or butyrate likely participates in such effects of commensal bacteria.

摘要

癌胚抗原相关细胞粘附分子(CEACAM)1和CEACAM20属于免疫球蛋白超家族成员,主要在肠上皮细胞(IECs)中表达,并共定位于这些细胞的顶端表面。我们在此表明,用抗革兰氏阳性菌的抗生素处理小鼠后,小肠IECs中小鼠CEACAM1和CEACAM20的mRNA和蛋白质水平表达均显著降低。与对照无特定病原体小鼠相比,无菌小鼠小肠IECs中这两种蛋白质的表达也降低。将肠类器官暴露于IFN-γ显著增加了CEACAM1或CEACAM20的表达,而暴露于TNF-α则增加了前者蛋白质的表达,但未增加后者的表达。相反,暴露于丁酸盐(一种由肠道细菌发酵产生的短链脂肪酸)后,肠类器官中CEACAM20的表达显著增加,而CEACAM1的表达未增加。总体而言,我们的结果表明革兰氏阳性菌促进小肠中CEACAM1或CEACAM20的mRNA表达。炎性细胞因子或丁酸盐可能参与共生细菌的这种作用。

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