title: Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats.
abstract: Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS-induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-time PCR analysis showed that the expression of miR-155 in lung tissue was greatly elevated in wild-type mice after LPS stimulation. In situ hybridization showed that miR-155 was mainly expressed in alveolar macrophages. In vitro experiments performed in isolated alveolar macrophages and polarized bone marrow-derived macrophages confirmed that miR-155 expression in macrophages was increased in response to LPS stimulation. Conversely, miR-155 gain-of-function in alveolar macrophages remarkably exaggerated LPS-induced acute lung injury. Molecular studies identified the inflammation repressor suppressor of cytokine signaling (SOCS-1) as the downstream target of miR-155. By binding to the 3'-UTR of the SOCS-1 mRNA, miR-155 downregulated SOCS-1 expression, thus, permitting the inflammatory response during lung injury. Finally, we generated a novel miR-155 knockout rat strain and showed that the proinflammatory role of miR-155 was conserved in rats. Our study identified miR-155 as a proinflammatory factor after LPS stimulation, and alveolar macrophages-derived miR-155 has an important role in LPS-induced ALI.
authors.affiliation: Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China;
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China; and.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Xiao-Wu
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: San-Xing
authors.initials: SX
authors.lastname: Bai
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China jinzhouzhang2006@126.com.
authors.forename: Jin-Zhou
authors.initials: JZ
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Shi-Qiang
authors.initials: SQ
authors.lastname: Yu
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000502:physiology*; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D017422:Sequence Analysis, DNA
chemical_list: D008070:Lipopolysaccharides; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse
keywords: CRISPR/Cas9; SOCS-1; acute lung injury; lipopolysacharide; micro-RNA-155