Up-regulated microRNA-146a negatively modulate Helicobacter pylori-induced inflammatory response in human gastric epithelial cells
Up-regulated microRNA-146a negatively modulate Helicobacter pylori-induced inflammatory response in human gastric epithelial cells
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上调的 microRNA-146a 负向调节幽门螺杆菌诱导的人胃上皮细胞炎症反应
DOI：
10.1016/j.micinf.2010.06.002
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发表时间：
2010-10-01
影响因子：
5.8
通讯作者：
Zou, Quanming
中科院分区：
文献类型：
--
作者：
Liu, Zhen;Xiao, Bin;Zou, Quanming
幽门螺杆菌(Hp)是人类胃粘膜的主要致病菌。然而，幽门螺杆菌诱导免疫应答的调控机制尚不清楚。MicroRNAs(MiRNAs)最近被认为是基因表达的关键转录后调节因子，而它们在幽门螺杆菌感染中的作用才刚刚开始探索。在这里，我们首次报道了幽门螺杆菌感染上调miR-146a在胃上皮细胞和胃粘膜组织中的表达，这是一种依赖于NF-kappa B的方式。反过来，miR-146a可能下调靶基因白介素1受体相关激酶1(IRAK1)和肿瘤坏死因子受体相关因子6(TRAF6)的表达。此外，miR-146a通过降低NF-kappa B的活性，负向调节幽门螺杆菌触发的白细胞介素8、生长相关癌基因α和巨噬细胞炎性蛋白3α。总之，幽门螺杆菌诱导的miR-146a通过靶向IRAK1和TRAF6，在负反馈环中发挥潜在作用，调节炎症反应。(C)2010年巴斯德研究所。爱思唯尔·马森公司出版。版权所有。
Helicobacter pylori (H. pylori) is a major human pathogenic bacterium in gastric mucosa. However, the regulatory mechanism of H. pylori-induced immune response is not clear. MicroRNAs (miRNAs) have recently emerged as key post-transcriptional regulators of gene expression, and their role in H. pylori infection is just beginning to be explored. Here, we first reported that H. pylori infection up-regulated the expression of miR-146a in gastric epithelial cells as well as in gastric mucosal tissues in NF-kappa B-dependent manner. In turn, miR-146a may downregulate the expression of target genes, interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6). Furthermore, miR-146a negatively regulated H. pylori-triggered interleukin (IL)-8, growth-related oncogene (GRO)-alpha, and macrophage inflammatory protein (MIP) -3 alpha through diminishing NF-kappa B activity. In conclusion, H. pylori-induced miR-146a plays a potential role in a negative feedback loop to modulate the inflammation by targeting IRAK1 and TRAF6. (C) 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.