A Salmonella enterica serovar typhimurium translocated leucine-rich repeat effector protein inhibits NF-kappa B-dependent gene expression.
A Salmonella enterica serovar typhimurium translocated leucine-rich repeat effector protein inhibits NF-kappa B-dependent gene expression.
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DOI：
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发表时间：
2003
影响因子：
3.1
通讯作者：
A. Haraga;Samuel I. Miller
中科院分区：
文献类型：
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作者：
A. Haraga;Samuel I. Miller
非伤寒沙门氏菌是一种肠道病原体，可引起急性胃肠炎，并在肠道内长期定植。在肠上皮细胞中，这些细菌诱导促炎细胞因子的分泌，如白介素8(IL-8)，从而通过募集多形核白细胞而导致深刻的炎症反应。沙门氏菌诱导产生IL-8。是由于转录因子核因子-kappaB(NF-kappa B)和激活蛋白-1(AP-1)的激活。这项工作表明，肠炎沙门氏菌血清型鼠伤寒沙门氏菌可以下调肠上皮细胞入侵后IL-8的产生。沙门氏菌易位效应蛋白SspH1和SptP参与了这一过程。SspH1是细菌LPX重复蛋白家族中的一员，定位于哺乳动物的细胞核，抑制依赖于核因子-kappa B的基因表达。福氏志贺氏菌易位效应蛋白IpaH9.8在哺乳动物细胞中具有相似的结构和亚细胞定位，也抑制依赖于NF-kappaB的基因表达。我们认为，细胞内的肠杆菌、鼠伤寒沙门氏菌和福氏志贺氏菌对炎症反应的抑制，有助于宿主组织的细菌定植和致病。
Nontyphoidal salmonellae are enteric pathogens that cause acute gastroenteritis and colonize the intestinal tract for prolonged periods. In the intestinal epithelia, these bacteria induce secretion of proinflammatory cytokines, such as interleukin-8 (IL-8), which leads to a profound inflammatory response through recruitment of polymorphonuclear leukocytes. Production of IL-8 induced by Salmonella spp. is due to the activation of the transcription factors nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1). This work demonstrates that Salmonella enterica serovar Typhimurium can downmodulate IL-8 production after invasion of intestinal epithelial cells. The Salmonella translocated effector proteins SspH1 and SptP participate in this process. SspH1 is a member of the bacterial LPX repeat protein family that localizes to the mammalian nucleus and inhibits NF-kappa B-dependent gene expression. A Shigella flexneri translocated effector, IpaH9.8, which has a similar structure and subcellular localization in mammalian cells, also inhibits NF-kappaB-dependent gene expression. We propose that suppression of inflammatory responses by intracellular S. enterica serovar Typhimurium, and perhaps Shigella flexneri, contributes to bacterial colonization of host tissues and pathogenesis.