title: MicroRNA-127 inhibits lung inflammation by targeting IgG Fcγ receptor I.
abstract: The molecular mechanisms of acute lung injury are incompletely understood. MicroRNAs (miRNAs) are crucial biological regulators that act by suppressing their target genes and are involved in a variety of pathophysiologic processes. miR-127 appears to be downregulated during lung injury. We set out to investigate the role of miR-127 in lung injury and inflammation. Expression of miR-127 significantly reduced cytokine release by macrophages. Looking into the mechanisms of regulation of inflammation by miR-127, we found that IgG FcγRI (CD64) was a target of miR-127, as evidenced by reduced CD64 protein expression in macrophages overexpressing miR-127. Furthermore, miR-127 significantly reduced the luciferase activity with a reporter construct containing the native 3' untranslated region of CD64. Importantly, we demonstrated that miR-127 attenuated lung inflammation in an IgG immune complex model in vivo. Collectively, these data show that miR-127 targets macrophage CD64 expression and promotes the reduction of lung inflammation. Understanding how miRNAs regulate lung inflammation may represent an attractive way to control inflammation induced by infectious or noninfectious lung injury.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
authors.forename: Jiurong
authors.initials: J
authors.lastname: Liang
authors.forename: Ningshan
authors.initials: N
authors.lastname: Liu
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Li
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
authors.forename: Dianhua
authors.initials: D
authors.lastname: Jiang
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000936:Antigen-Antibody Complex / Q000633:toxicity; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D018390:Gene Targeting / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D016180:Lentivirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D011024:Pneumonia, Viral / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D000936:Antigen-Antibody Complex; D016207:Cytokines; C489017:FCGR1A protein, human; C485701:Fcgr1 protein, mouse; D018836:Inflammation Mediators; D035683:MicroRNAs; C533109:Mirn127 microRNA, mouse; D017452:Receptors, IgG