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miR-155 通过靶向 Rheb 抑制铜绿假单胞菌诱导的角膜炎中的细菌清除。

miR-155 suppresses bacterial clearance in Pseudomonas aeruginosa-induced keratitis by targeting Rheb.

出版信息

J Infect Dis. 2014 Jul 1;210(1):89-98. doi: 10.1093/infdis/jiu002. Epub 2014 Jan 7.

DOI:10.1093/infdis/jiu002
PMID:24403554
Abstract

miR-155 (microRNA-155) is an important noncoding RNA in regulating host inflammatory responses. However, its regulatory role in ocular infection remains unclear. Our study first explored the function of miR-155 in Pseudomonas aeruginosa-induced keratitis, one of the most common sight-threatening ocular diseases. We found that miR-155 expression was enhanced in human and mouse corneas after P. aeruginosa infection and was mainly expressed in macrophages but not neutrophils. In vivo studies demonstrated that miR-155 knockout mice displayed more resistance to P. aeruginosa keratitis, with a higher inducible nitric oxide synthase level and a lower bacterial burden. More importantly, in vitro data indicated that miR-155 suppressed the macrophage-mediated bacterial phagocytosis and intracellular killing of P. aeruginosa by targeting Rheb (Ras homolog enriched in brain). To the best of our knowledge, this is the first study to explore the role of miR-155 in bacterial keratitis, which may provide a promising target for clinical treatment of P. aeruginosa keratitis and other infectious diseases.

摘要

miR-155(microRNA-155)是一种在调节宿主炎症反应中起重要作用的非编码 RNA。然而,其在眼部感染中的调节作用尚不清楚。我们的研究首次探讨了 miR-155 在铜绿假单胞菌诱导的角膜炎中的作用,铜绿假单胞菌角膜炎是最常见的威胁视力的眼部疾病之一。我们发现,在铜绿假单胞菌感染后,人眼和鼠眼的 miR-155 表达增强,主要在巨噬细胞中表达,而不是中性粒细胞中表达。体内研究表明,miR-155 敲除小鼠对铜绿假单胞菌角膜炎的抵抗力更强,诱导型一氧化氮合酶水平更高,细菌负荷更低。更重要的是,体外数据表明,miR-155 通过靶向 Rheb(富含大脑的 Ras 同源物)抑制巨噬细胞介导的铜绿假单胞菌吞噬和细胞内杀伤。据我们所知,这是首次研究 miR-155 在细菌性角膜炎中的作用,这可能为铜绿假单胞菌角膜炎和其他感染性疾病的临床治疗提供有希望的靶点。

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