Interleukin-2 receptor β subunit-dependent and -independent regulation of intestinal epithelial tight junctions
Interleukin-2 receptor β subunit-dependent and -independent regulation of intestinal epithelial tight junctions
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DOI：
10.1074/jbc.m106013200
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发表时间：
2001-09-21
影响因子：
4.8
通讯作者：
Reinecker, HC
中科院分区：
文献类型：
--
作者：
Nishiyama, R;Sakaguchi, T;Reinecker, HC
白细胞介素-15能够调节肠上皮细胞紧密连接的形成。然而，调节肠道屏障功能响应IL-15的机制以及IL-15配体受体系统的相关亚基尚不清楚。我们检测了人肠上皮细胞系T-84中IL-2R β亚基和il -15依赖的紧密连接相关蛋白的调控。IL-2R β亚基在肠上皮细胞中表达并诱导信号转导。il -15介导的肠上皮单分子层收紧与紧密连接蛋白向Triton x -100不溶性蛋白组分的增强募集相关。IL-15介导的ZO-1和ZO-2表达上调与IL-2R β亚基无关，而IL-15对occludin的磷酸化和增强claudin-1和claudin-2的膜结合需要IL-2R β亚基的存在。claudin和高磷酸化occludin被募集到紧密连接中，导致肠上皮细胞中紧密连接形成的诱导比ZO-1和ZO-2本身的上调更明显。IL-15对肠上皮屏障功能的调节涉及IL-2R β依赖和非依赖的信号通路，导致cludin、高磷酸化occludin、ZO-1和ZO-2聚集到紧密连接蛋白复合体中。
Interleukin (IL)-15 is able to regulate tight junction formation in intestinal epithelial cells. However, the mechanisms that regulate the intestinal barrier function in response to IL-15 and the involved subunits of the IL-15 ligand-receptor system are unknown. We determined the IL-2R beta subunit and IL-15-dependent regulation of tight junction-associated proteins in the human intestinal epithelial cell line T-84. The IL-2R beta subunit was expressed and induced signal transduction in caveolin enriched rafts in intestinal epithelial cells. IL-15-mediated tightening of intestinal epithelial monolayers correlated with the enhanced recruitment of tight junction proteins into Triton X-100-insoluble protein fractions. IL-15-mediated up-regulation of ZO-1 and ZO-2 expression was independent of the IL-2R beta subunit, whereas the phosphorylation of occludin and enhanced membrane association of claudin-1 and claudin-2 by IL-15 required the presence of the IL-2R beta subunit. Recruitment of claudins and hyperphosphorylated occludin into tight junctions resulted in a more marked induction of tight junction formation in intestinal epithelial cells than the up-regulation of ZO-1 and ZO-2 by itself. The regulation of the intestinal epithelial barrier function by IL-15 involves IL-2R beta -dependent and -independent signaling pathways leading to the recruitment of claudins, hyperphosphorylated occludin, ZO-1, and ZO-2 into the tight junctional protein complex.