Disruption of tight junctions and induction of proinflammatory cytokine responses in colonic epithelial cells by Campylobacter jejuni
Disruption of tight junctions and induction of proinflammatory cytokine responses in colonic epithelial cells by Campylobacter jejuni
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DOI：
10.1128/iai.00958-06
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发表时间：
2006-12-01
影响因子：
3.1
通讯作者：
Schauer, David B.
中科院分区：
文献类型：
--
作者：
Chen, Ming L.;Ge, Zhongming;Schauer, David B.
空肠弯曲杆菌是人类小肠结肠炎的主要原因，并与感染后并发症（包括肠易激综合征和格林-巴利综合征）有关。然而，C.空肠感染仍然知之甚少。肠上皮细胞中的细胞旁途径由细胞间连接（紧密连接和粘附连接）门控，从而在固有层中的管腔微生物和宿主免疫细胞之间提供功能屏障。在这里，我们描述了C。空肠感染极化T84单层的顶端感染引起跨上皮电阻（TER）的时间依赖性降低。免疫荧光显微镜显示的紧密连接跨膜蛋白occludin从细胞间的细胞内位置的重新分配。使用平衡蔗糖密度梯度的亚细胞分级分离表明，在顶端感染后，脂筏、Triton X-100可溶性组分和Triton X-100不溶性颗粒中的过度磷酸化闭合蛋白减少。根尖感染C.空肠还引起NF-κ B和AP-1的快速活化，细胞外信号调节激酶、Jun N-末端蛋白激酶和p38促分裂原活化蛋白激酶的磷酸化，以及CXC趋化因子白细胞介素-8（IL-8）的基底外侧分泌。基底外侧感染C.空肠引起TER更快的下降，紧密连接蛋白的可比较的再分布，和分泌更多的IL-8比与顶端感染。这些结果表明，屏障功能受损和趋化因子表达增加导致了念珠菌的发病机制。空肠诱导的小肠结肠炎
Campylobacter jejuni is a leading cause of human enterocolitis and is associated with postinfectious complications, including irritable bowel syndrome and Guillain-Barre syndrome. However, the pathogenesis of C. jejuni infection remains poorly understood. Paracellular pathways in intestinal epithellial cells are gated by intercellular junctions (tight junctions and adherens junctions), providing a functional barrier between luminal microbes and host immune cells in the lamina propria. Here we describe alterations in tight junctions in intestinal epithelial monolayers following C. jejuni infection. Apical infection of polarized T84 monolayers caused a time-dependent decrease in transepithelial electrical resistance (TER). Immunofluorescence microscopy revealed a redistribution of the tight junctional transmembrane protein occludin from an intercellullar to an intracellular location. Subcellular fractionation using equilibrium sucrose density gradients demonstrated decreased hyperphosphorylated occludin in lipid rafts, Triton X-100-soluble fractions, and the Triton X-100-insoluble pellet following apical infection. Apical infection with C. jejuni also caused rapid activation of NF-kappa B and AP-1, phosphorylation of extracellular signal-regulated kinase, Jun N-terminal protein kinase, and p38 mitogen-activated protein kinases, and basolateral secretion of the CXC chemokine interieukin-8 (IL-8). Basolateral infection with C. jejuni caused a more rapid decrease in TER, comparable redistribution of tight-junction proteins, and secretion of more IL-8 than that seen with apical infection. These results suggest that compromised barrier function and increased chemokine expression contribute to the pathogenesis of C. jejuni-induced enterocolitis.