title: Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury.
abstract: Despite the critical role of microRNA in inflammatory response, little is known about its function in inflammation-induced Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS). To investigate the potential role of microRNA146a (miR-146a) in ALI, we used lipopolysaccharide (LPS)-induced ALI rat model. Our data revealed that LPS-induced lung injury in rats resulted in significant upregulation of proinflammatory cytokine tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β, and miR-146a expression. LPS treatment also leads to higher expression of miR-146a as well as increase in secretion of TNF-α, IL-6, and IL-1β in alveolar macrophage (AM) NR8383 cells in a time-dependent manner. Manipulation with miR146a mimic significantly suppressed LPS-mediated TNF-α, IL-6, and IL-1β induction in NR8383 cells by repressing expression of IRAK-1 and TRAF-6. These data clearly indicate that the upregulation of miR146a suppresses inflammatory mediators in LPS induced-ALI model. Therefore, miR-146a may be therapeutically targeted as a mean to repress inflammatory response following ALI.
authors.affiliation: Critical Care Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Zeng
authors.forename: Honghan
authors.initials: H
authors.lastname: Gong
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Kemin
authors.initials: K
authors.lastname: Jie
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Ding
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shao
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.forename: Yian
authors.initials: Y
authors.lastname: Zhan
authors.forename: Cheng
authors.initials: C
authors.lastname: Nie
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhu
authors.forename: Kejian
authors.initials: K
authors.lastname: Qian
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; C554180:MIRN146 microRNA, rat; D035683:MicroRNAs; D048029:TNF Receptor-Associated Factor 6; D014409:Tumor Necrosis Factor-alpha; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases