A DISTINCT ARRAY OF PROINFLAMMATORY CYTOKINES IS EXPRESSED IN HUMAN COLON EPITHELIAL-CELLS IN RESPONSE TO BACTERIAL INVASION
A DISTINCT ARRAY OF PROINFLAMMATORY CYTOKINES IS EXPRESSED IN HUMAN COLON EPITHELIAL-CELLS IN RESPONSE TO BACTERIAL INVASION
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DOI：
10.1172/jci117676
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发表时间：
1995-01-01
影响因子：
15.9
通讯作者：
KAGNOFF, MF
中科院分区：
文献类型：
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作者：
JUNG, HC;ECKMANN, L;KAGNOFF, MF
穿透肠上皮屏障的病原菌刺激邻近肠粘膜中的炎症反应。目前的研究询问结肠上皮细胞是否可以提供对急性粘膜炎症反应的启动和放大重要的信号。人结肠上皮细胞系单层的感染（T84、HT 29、Caco-2）与侵袭性细菌菌株（都柏林沙门氏菌，志贺氏菌，小肠结肠炎耶尔森氏菌，单核细胞增生李斯特菌，肠侵袭性大肠杆菌）导致四种促炎细胞因子，IL-8，单核细胞趋化蛋白-1，GM-CSF和TNF α的特定阵列的协调表达和上调，通过mRNA水平和细胞因子分泌来评估。在TNF α或IL-1刺激这些细胞后，相同细胞因子的表达上调。相反，细胞因子基因表达在结肠上皮细胞被非侵袭性细菌或非侵袭性原生动物寄生虫G.兰布利亚值得注意的是，没有细胞系响应于相同的刺激而表达IL-2、IL-4、IL-5、IL-6、IL-12 p40、IFN-γ的mRNA或显著水平的IL-1或IL-10。IL-8、MCP-1、GM-CSF和TNF α的协同表达似乎是人结肠上皮细胞的一般特性，因为新鲜分离的人结肠上皮细胞也表达相同的细胞因子阵列以及IL-6。由于响应于细菌入侵或其他促炎激动剂而表达的细胞因子在炎症细胞的趋化性和活化中具有充分记载的作用，因此结肠上皮细胞似乎被编程为在微生物入侵后的最早阶段提供一组用于活化粘膜炎症反应的信号。
Pathogenic bacteria that penetrate the intestinal epithelial barrier stimulate an inflammatory response in the adjacent intestinal mucosa. The present studies asked whether colon epithelial cells can provide signals that are important for the initiation and amplification of an acute mucosal inflammatory response. Infection of monolayers of human colon epithelial cell lines (T84, HT29, Caco-2) with invasive strains of bacteria (Salmonella dublin, Shigella dysenteriae, Yersinia enterocolitica, Listeria monocytogenes, enteroinvasive Escherichia coli) resulted in the coordinate expression and upregulation of a specific array of four proinflammatory cytokines, IL-8, monocyte chemotactic protein-1, GM-CSF, and TNF alpha, as assessed by mRNA levels and cytokine secretion. Expression of the same cytokines was upregulated after TNF alpha or IL-1 stimulation of these cells. In contrast, cytokine gene expression was not altered after infection of colon epithelial cells with noninvasive bacteria or the noninvasive protozoan parasite, G. lamblia. Notably, none of the cell lines expressed mRNA for IL-2, IL-4, IL-5, IL-6, IL-12p40, IFN-gamma, or significant levels of IL-1 or IL-10 in response to the identical stimuli. The coordinate expression of IL-8, MCP-1, GM-CSF and TNF alpha appears to be a general property of human colon epithelial cells since an identical array of cytokines, as well as IL-6, also was expressed by freshly isolated human colon epithelial cells. Since the cytokines expressed in response to bacterial invasion or other proinflammatory agonists have a well documented role in chemotaxis and activation of inflammatory cells, colon epithelial cells appear to be programmed to provide a set of signals for the activation of the mucosal inflammatory response in the earliest phases after microbial invasion.