The hemorrhagic coli pilus (HCP) of Escherichia coli O157:H7 is an inducer of proinflammatory cytokine secretion in intestinal epithelial cells.
The hemorrhagic coli pilus (HCP) of Escherichia coli O157:H7 is an inducer of proinflammatory cytokine secretion in intestinal epithelial cells.
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DOI：
10.1371/journal.pone.0012127
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发表时间：
2010-08-12
期刊：
影响因子：
3.7
通讯作者：
Xicohtencatl-Cortes J
中科院分区：
文献类型：
--
作者：
Ledesma MA;Ochoa SA;Cruz A;Rocha-Ramírez LM;Mas-Oliva J;Eslava CA;Girón JA;Xicohtencatl-Cortes J
肠出血性大肠杆菌（EHEC）O 157：H7是出血性结肠炎和溶血性尿毒综合征（HUS）的病原体，产生长束IV型皮利（TFP），称为出血性大肠杆菌皮利（HCP）。HCP能够介导与致病性相关的几种现象：i）粘附于人和牛上皮细胞; ii）上皮细胞的侵入; iii）兔红细胞的血凝; iv）生物膜形成; v）抽搐运动性;和vi）与层粘连蛋白和纤连蛋白的特异性结合。HCP由19 kDa的菌毛蛋白亚基（HcpA）组成，该亚基由hcpA染色体基因（在大肠杆菌中称为前菌毛蛋白肽酶依赖基因[ppdD]）编码。coli K-12）。在这项研究中，我们探讨了HCP的潜在作用，E。coli O 157：H7菌株EDL 933激活多种宿主上皮细胞释放促炎和抗炎细胞因子。我们发现纯化的HCP和重组HcpA蛋白诱导培养的极化肠细胞（T84和HT-29细胞）和非肠HeLa细胞显著释放IL-8和TNF-α。在HCP和重组HcpA存在下，与≥50 ng/ml蛋白孵育6 h后，促炎性IL-8和TNF-α水平升高，但IL-2、IL-6或IL-10细胞因子水平未升高，表明IL-8和TNF-α的刺激具有剂量和时间依赖性。此外，我们还证明了鞭毛是细胞因子产生的有效诱导剂。此外，MAPK激活动力学研究表明，EHEC诱导HCP产生条件下的p38磷酸化，ERK 1/2和JNK激活后3小时的EHEC感染可检测到。用HT-29细胞的表皮生长因子刺激HT-29细胞30分钟，导致三种MAPK的活化。由EHEC O 157：H7产生的HCP的HcpA菌毛蛋白单体是IL-8和TNF-α释放的强效诱导剂，这一事件在由该病原体引起的出血性结肠炎的发病机制中可能起重要作用。
Enterohemorrhagic Escherichia coli (EHEC) O157:H7, the causative agent of hemorrhagic colitis and the hemolytic uremic syndrome (HUS), produces long bundles of type IV pili (TFP) called hemorrhagic coli pili (HCP). HCP are capable of mediating several phenomena associated with pathogenicity: i) adherence to human and bovine epithelial cells; ii) invasion of epithelial cells; iii) hemagglutination of rabbit erythrocytes; iv) biofilm formation; v) twitching motility; and vi) specific binding to laminin and fibronectin. HCP are composed of a 19 kDa pilin subunit (HcpA) encoded by the hcpA chromosomal gene (called prepilin peptidase-dependent gene [ppdD] in E. coli K-12). In this study we investigated the potential role of HCP of E. coli O157:H7 strain EDL933 in activating the release of pro- and anti-inflammatory cytokines from a variety of host epithelial cells. We found that purified HCP and a recombinant HcpA protein induced significant release of IL-8 and TNF-α, from cultured polarized intestinal cells (T84 and HT-29 cells) and non-intestinal HeLa cells. Levels of proinflammatory IL-8 and TNF-α, but not IL-2, IL6, or IL-10 cytokines, were increased in the presence of HCP and recombinant HcpA after 6 h of incubation with ≥50 ng/ml of protein, suggesting that stimulation of IL-8 and TNF-α are dose and time-dependent. In addition, we also demonstrated that flagella are potent inducers of cytokine production. Furthermore, MAPK activation kinetics studies showed that EHEC induces p38 phosphorylation under HCP-producing conditions, and ERK1/2 and JNK activation was detectable after 3 h of EHEC infection. HT-29 cells were stimulated with epidermal growth factor stimulation of HT-29 cells for 30 min leading to activation of three MAPKs. The HcpA pilin monomer of the HCP produced by EHEC O157:H7 is a potent inducer of IL-8 and TNF-α release, an event which could play a significant role in the pathogenesis of hemorrhagic colitis caused by this pathogen.
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