Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells
Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells
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DOI：
10.1053/gast.2002.30329
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发表时间：
2002-01-01
期刊：
影响因子：
29.4
通讯作者：
Reinecker, HC
中科院分区：
文献类型：
--
作者：
Brand, S;Sakaguchi, T;Reinecker, HC
背景和目标：在这项研究中，我们确定了在人肠上皮细胞中配体特异性激活Fractalkine受体CX 3CR 1后的信号转导和功能后果。研究方法：通过免疫组化、免疫印迹和逆转录聚合酶链反应测定人结肠组织和肠上皮细胞系中CX 3CR 1的表达。丝裂原活化蛋白激酶（MAPK）激活的调节通过免疫印迹法进行评估。通过北方印迹法测定趋化因子信使RNA（mRNA）表达的调节。NF-κ B和p53活化通过电迁移率变化测定来评估。结果如下：Fractalkine介导MEK-1和Galphai依赖但不依赖于磷脂酰肌醇-3-激酶的细胞外信号调节激酶-MAPK的激活。Fractalkine激活NF-κ B和p53，导致白细胞介素8和Fractalkine mRNA表达。CX 3CR 1介导的肠上皮细胞活化能够诱导人中性粒细胞迁移进入但不通过肠上皮细胞单层。结论：CX 3CR 1介导肠上皮细胞的不同功能反应，包括细胞存活信号的自分泌调节和免疫调节剂的激活，表明CX 3CR 1在源自肠上皮的宿主防御机制中的作用。
Background & Aims: In this study, we determined the signal transduction and functional consequences after ligand-specific activation of the fractalkine receptor CX3CR1 in human intestinal epithelial cells. Methods: CX3CR1 expression in human colonic tissues and intestinal epithelial cell lines was determined by immunohistochemistry, immunoblotting, and reverse-transcription polymerase chain reaction. The regulation of mitogen-activated protein kinase (MAPK) activation was assessed by immunoblotting. Regulation of chemokine messenger RNA (mRNA) expression was determined by Northern blotting. NF-kappaB and p53 activation was assessed by electromobility shift assays. Results: Fractalkine mediated the MEK-1 and Galphai-dependent but phosphatidylinositol-3-kinase-independent activation of extracellular signal-regulated kinase-MAPK. Fractalkine activated NF-kappaB and p53 resulting in interleukin 8 and fractalkine mRNA expression. CX3CR1-mediated activation of intestinal epithelial cells was able to induce migration of human neutrophils into but not through the intestinal epithellal cell monolayer. Conclusions: CX3CR1 mediates distinct functional responses in intestinal epithelial cells, which include the autocrine regulation of cell-survival signals and activation of immune modulators, indicating a role of CX3CR1 in host defense mechanisms originating from the intestinal epithelium.