title: H. pylori related proinflammatory cytokines contribute to the induction of miR-146a in human gastric epithelial cells.
abstract: MicroRNAs have been implicated as a central regulator of the immune system. We have previously reported that Helicobacter pylori (H. pylori) was able to increase the expression of miR-146a, and miR-146a may negatively regulate H. pylori-induced inflammation, but the exact mechanism of how H. pylori contribute the induction of miR-146a is not clear. Here, we attempted to assess the role of H. pylori related proinflammatory cytokines including interleukin (IL)-8, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β, and cytotoxin-associated gene A (CagA) virulence factor on the induction of miR-146a. We found that IL-8, TNF-α, and IL-1β could contribute to the induction of miR-146a in gastric epithelial cell HGC-27 in NF-κB-dependent manner, while the induction of miR-146a upon H. pylori stimulation was independent of above proinflammatory cytokines. Furthermore, overexpression of miR-146a reduced H. pylori-induced IL-8, TNF-α, and IL-1β. However, CagA had no effect on the miR-146a induction. Taken together, our study suggest that proinflammatory cytokines IL-8, TNF-α, and IL-1β could contribute to the induction of miR-146a during H. pylori infection, while CagA is not necessarily required for miR-146a induction. miR-146a may function as novel negative regulators to modulate the inflammation.
authors.affiliation: Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Xiao
authors.forename: En-Dong
authors.initials: ED
authors.lastname: Zhu
authors.forename: Bo-Sheng
authors.initials: BS
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.forename: Quan-Ming
authors.initials: QM
authors.lastname: Zou
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Liang
authors.forename: Xu-Hu
authors.initials: XH
authors.lastname: Mao
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013270:Stomach / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D018836:Inflammation Mediators; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C080866:cagA protein, Helicobacter pylori