Requirement of epithelial integrin-linked kinase for facilitation of Citrobacter rodentium-induced colitis.
Requirement of epithelial integrin-linked kinase for facilitation of Citrobacter rodentium-induced colitis.
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DOI：
10.1186/1471-230x-13-137
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发表时间：
2013-09-11
影响因子：
2.4
通讯作者：
Salh B
中科院分区：
文献类型：
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作者：
Assi K;Bergstrom K;Vallance B;Owen D;Salh B
整合素连接的激酶(ILK)是一种丝氨酸-苏氨酸激酶，它将细胞外基质相关信号转化为细胞内信号，在细胞运动、发育和癌症中发挥重要作用。最近研究表明，ILK通过ILK-细菌OSPE结合在细菌上皮细胞的附着中起重要作用。在这里，我们报告了上皮源性ILK在响应轮状柠檬酸杆菌感染中的作用。给正常小鼠和肠上皮细胞基因敲除小鼠灌胃罗丹参。用酶联免疫吸附试验和RT-PCR方法测定小鼠结肠组织炎症评分和细胞因子水平。将细菌定植于MacConkey琼脂上，并用抗内毒素和抗TIR抗体进行免疫荧光显微镜观察。ILK-KO小鼠在感染后15天体重减轻(p <； 0.01)，组织学炎症评分降低(p <； 0.01)，CCL2和促炎细胞因子减少。这不是由于减少了定殖率，而是与轮状芽胞杆菌细菌迁移模式的改变有关。在ILK-KO小鼠中发现纤维连接蛋白表达减弱。在活体中，轮状芽孢杆菌暴露可增加细胞系和小鼠上皮中ILK的表达。在ILK-KO小鼠中，观察到ser473Akt的激活减少，隐窝增殖减少，细胞周期蛋白D1的表达减少。ILK影响宿主对轮状芽胞杆菌诱导的感染的反应，而不依赖于ILK基因敲除小鼠中减少的定植。该组炎症减轻和对感染的增生性隐窝反应显著减弱，至少部分是CCL2和Cyclin D1表达分别减少的结果。
Integrin-linked kinase (ILK) is a serine-threonine kinase that transduces extracellular matrix-related cues into intracellular signals, with fundamental roles in cell motility, development and cancer. Recently ILK been shown to have an important role in bacterial epithelial cell attachment, through ILK-bacterial OspE binding. Here we report on the role of epithelial derived ILK in response to Citrobacter rodentium infection. C. rodentium was administered to both control and intestinal epithelial cell ILK knockout mice. Histological inflammatory scores were assessed, and cytokines measured by ELISA as well as RT-PCR, in mouse colons. Bacterial colonization was determined by plating homogenates onto MacConkey agar, and immunofluorescence microscopy performed using anti-LPS and anti-Tir antibodies. ILK-ko mice exhibited reduced weight loss at 15 days post-infection (p < 0.01) and demonstrated reduced histological inflammatory scores (p < 0.01), reduced CCL2 and pro-inflammatory cytokines. This was not due to reduced colonization, but was associated with an altered pattern of C. rodentium bacterial migration. Attenuated fibronectin expression was found in the ILK-ko mice. C. rodentium exposure was shown to increase ILK expression in cell lines, and in murine epithelium in vivo. In ILK-ko mice reduced activation of ser473Akt and reduced crypt proliferation, together with reduced cyclin D1 expression were observed. ILK influences the host response to C. rodentium -induced infection, independently of reduced colonization in the ILK knockout mice. The reduced inflammation and dramatically attenuated hyperplastic cryptal response to infection in this group, are at least in part the result of, the reduction in CCL2 and cyclin D1 expression respectively.