Epithelial cells secrete interleukin-8 in response to adhesion and invasion of diffusely adhering Escherichia coli lacking Afa/Dr genes

Epithelial cells secrete interleukin-8 in response to adhesion and invasion of diffusely adhering Escherichia coli lacking Afa/Dr genes
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DOI:
10.1111/j.1348-0421.2006.tb03781.x
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发表时间:
2006-01-01
影响因子:
2.6
通讯作者:
Nishikawa, Y
Nishikawa, Y
中科院分区:
医学4区
文献类型:
--
作者:
Meraz, IM;Arikawa, K;Nishikawa, Y

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稀疏粘附在人上皮细胞上的大肠杆菌被称为弥漫性粘附大肠杆菌(DAEC),现在已经了解了Afa/Dr粘附素家族的作用。不具有Afa的菌株。然而,它们还包括另一组DAEC,其致病性尚不清楚。诱导肠上皮细胞分泌白细胞介素-8 (IL-8)的能力可能是肠毒性细菌的一个特征。我们之前发现一些Afa/Dr DAEC菌株通过鞭毛刺激上皮细胞诱导IL-8。本研究检验了非afa /Dr DAEC是否能诱导上皮细胞(HEp-2、INT407和T84)中的IL-8。在21株菌株中,有11株(52%;11/21)诱导IL-8的水平与Afa/Dr DAEC高诱导剂菌株相当。黏附性在高、低诱导剂间无显著差异;因此,仅弥漫性粘附可能不足以诱导IL-8。结果表明,IL-8诱导与胞内细菌数量直接相关。Wortmannin是一种磷脂酰肌醇-3-磷酸激酶抑制剂,可减少细胞内细菌和IL-8的分泌。活性菌株在高诱导剂(10/11)中显著高于低诱导剂(4/10)。而4种低侵袭性菌株虽然具有运动性,但对IL-8几乎没有诱导作用。总之,一些非afa /Dr DAEC可诱导高水平的炎症细胞因子。然而,与Afa/Dr DAEC不同,非Afa/Dr菌株可能需要入侵才能引起强诱导。这些非afa /Dr高诱导剂因其细胞因子诱导特性而具有肠致病性。
Escherichia coli that sparsely adhere to human epithelial cells are known as diffusely adherent E. coli (DAEC), and the role of the Afa/Dr family of adhesins is now understood. Strains that do not possess Afa./Dr, however, comprise another group of DAEC, of which the pathogenicity remains unknown. The ability to induce interleukin-8 (IL-8) secretion from intestinal epithelial cells might be a feature of enterovirulent bacteria. We previously found that some Afa/Dr DAEC strains induce IL-8 by stimulating epithelial cells with flagella. The present study examines whether non-Afa/Dr DAEC can induce IL-8 in epithelial cells (HEp-2, INT407, and T84). Among 21 strains, 11 (52%; 11/21) induced as much IL-8 as high inducer strains of Afa/Dr DAEC. Adhesion did not significantly differ between high and low inducers; therefore diffuse adhesion alone is probably insufficient to induce IL-8. It was shown that IL-8 induction and the number of intracellular bacteria directly correlated. Wortmannin, an inhibitor of the phosphatidylinositol-3-phosphate kinase, reduced both intracellular bacteria and IL-8 secretion. Motile strains were significantly more prevalent among high (10/11) than low (4/10) inducers. However, 4 low invasive strains hardly induced IL-8 despite their motility. In conclusion, some non-Afa/Dr DAEC invoke the induction of high levels of inflammatory cytokines. Unlike Afa/Dr DAEC, however, non-Afa/Dr strains may require invasion to cause strong induction. These non-Afa/Dr high inducers can be enteropathogenic for the cytokine-inducing properties.