title: Contribution of CFTR to alveolar fluid clearance by lipoxin A4 via PI3K/Akt pathway in LPS-induced acute lung injury.
abstract: The lipoxins are the first proresolution mediators to be recognized and described as the endogenous "braking signals" for inflammation. We evaluated the anti-inflammatory and proresolution bioactions of lipoxin A4 in our lipopolysaccharide (LPS-)induced lung injury model. We demonstrated that lipoxin A4 significantly improved histology of rat lungs and inhibited IL-6 and TNF- α in LPS-induced lung injury. In addition, lipoxin A4 increased alveolar fluid clearance (AFC) and the effect of lipoxin A4 on AFC was abolished by CFTRinh-172 (a specific inhibitor of CFTR). Moreover, lipoxin A4 could increase cystic fibrosis transmembrane conductance regulator (CFTR) protein expression in vitro and in vivo. In rat primary alveolar type II (ATII) cells, LPS decreased CFTR protein expression via activation of PI3K/Akt, and lipoxin A4 suppressed LPS-stimulated phosphorylation of Akt. These results showed that lipoxin A4 enhanced CFTR protein expression and increased AFC via PI3K/Akt pathway. Thus, lipoxin A4 may provide a potential therapeutic approach for acute lung injury.
authors.affiliation: Department of Anesthesia and Critical Care, Second Affiliated Hospital of Wenzhou Medical College, 109 Xueyuan Road, Wenzhou, Zhejiang 325027, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Cheng
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Lian
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Qi
authors.forename: De-Rong
authors.initials: DR
authors.lastname: Wu
authors.forename: Xia
authors.initials: X
authors.lastname: Zheng
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Liu
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Li
authors.forename: Sheng-Wei
authors.initials: SW
authors.lastname: Jin
authors.forename: Fang Gao
authors.initials: FG
authors.lastname: Smith
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015153:Blotting, Western; D002478:Cells, Cultured; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D044045:Lipoxins / Q000627:therapeutic use*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D008070:Lipopolysaccharides; D044045:Lipoxins; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt