Uropathogenic Escherichia coli potentiates type 1 pilus-induced apoptosis by suppressing NF-κB
Uropathogenic Escherichia coli potentiates type 1 pilus-induced apoptosis by suppressing NF-κB
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DOI：
10.1128/iai.69.11.6689-6695.2001
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发表时间：
2001-11-01
影响因子：
3.1
通讯作者：
Schaeffer, AJ
中科院分区：
文献类型：
--
作者：
Klumpp, DJ;Weiser, AC;Schaeffer, AJ
尿路感染（UTI）是最常见的炎症性疾病之一。急性尿路感染通常由 1 型毛状大肠杆菌引起，并导致尿路上皮细胞凋亡、局部细胞因子释放和中性粒细胞浸润。为了检查尿路上皮细胞凋亡反应，将人尿路上皮细胞系与各种大肠杆菌分离株一起孵育，然后通过流式细胞术进行表征。尿路致病性大肠杆菌 (UPEC) 诱导尿路上皮快速凋亡，这种凋亡严格依赖于 1 型菌毛介导的相互作用。有趣的是，表达 I 型菌毛的非致病性 HB101 大肠杆菌诱导的细胞凋亡约为 UPEC 诱导水平的 50%，这表明致病菌株通过菌毛独立机制促进细胞凋亡。与这种可能性一致，UPEC 阻断了 NF-κB 依赖性报告基因对炎症刺激的反应，但这种作用与功能性 I 型菌毛无关，并且不是由实验室大肠杆菌菌株介导的。 UPEC 通过稳定 I kappaB α 来抑制 NF-kappaB，并且 UPEC 迅速改变细胞信号传导途径。最后，阻断 NF-kappaB 活性将 pilied HB101 诱导的细胞凋亡水平提高到 UPEC 诱导的细胞凋亡水平。这些结果表明 UPEC 阻断 NF-kappaB，从而增强 1 型菌毛诱导的细胞凋亡，作为泌尿道致病程序的一个组成部分。
Urinary tract infections (UTIs) are among the most common inflammatory diseases. Acute UTIs are typically caused by type 1-piliated Escherichia coli and result in urothelial apoptosis, local cytokine release, and neutrophil infiltration. To examine the urothelial apoptotic response, a human urothelial cell line was incubated with various E. coli isolates and was then characterized by flow cytometry. Uropathogenic E. coli (UPEC) induced rapid urothelial apoptosis that was strictly dependent upon interactions mediated by type 1 pili. Interestingly, nonpathogenic HB101 E. coli expressing type I pili induced apoptosis at approximately 50% of the level induced by UPEC, suggesting that pathogenic strains contribute to apoptosis by pilus-independent mechanisms. Consistent with this possibility, UPEC blocked activity of an NF-kappaB-dependent reporter in response to inflammatory stimuli, yet this effect was independent of functional type I pili and was not mediated by laboratory strains of E. coli. UPEC suppressed NF-kappaB by stabilizing I kappaB alpha., and UPEC rapidly altered cellular signaling pathways. Finally, blocking NF-kappaB activity increased the level of piliated HB101-induced apoptosis to the level of apoptosis induced by UPEC. These results suggest that UPEC blocks NF-kappaB and thereby enhances type 1 pili-induced apoptosis as a component of the uropathogenic program.