title: Effect of exogenous surfactant on phosphatidylinositol 3-kinase-Akt pathway and peroxisome proliferator activated receptor-γ during endotoxin induced acute respiratory distress syndrome.
abstract: Lipopolysaccharide induced acute respiratory distress syndrome (ARDS) leads to an unacceptably high mortality. In this regard, the anti-inflammatory properties of surfactant may provide a therapeutic option. Phosphoinositide 3-kinase (PI3-K) and the downstream serine/threonine kinase Akt/protein kinase B have a central role in modulating neutrophil function, including respiratory burst, chemotaxis, and apoptosis. This study explores the mechanisms of surfactant dependent protection by regulating PPAR-γ in a rat model of ARDS. Sprague-Dawley male rats were divided into four groups: buffer controls; rats challenged with LPS (055:B5 E. coli); challenged with LPS and treated with porcine surfactant; and challenged with LPS and treated with synthetic surfactant. Expression of PI3-K, Akt, GSK3-β, and PPAR-γ were studied by western immunoblot, immunofluorescence and by immunohistochemistry. In vivo endotoxin administration to rat resulted in activation of PI3-K and Akt in the lungs. The severity of endotoxemia-induced ALI was significantly diminished in rat with surfactant administration. Similar results were also seen in PPAR-γ expression. These results show that PI3-K occupies a central position in regulating endotoxin-induced ALI involving inflammatory responses. Surfactant treatment conferred protection in rat model dependent on PPAR-γ and inhibition of PI3-K/Akt pathway.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Mittal
authors.forename: Sankar Nath
authors.initials: SN
authors.lastname: Sanyal
mesh_terms: D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D047495:PPAR gamma / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine
chemical_list: D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D008070:Lipopolysaccharides; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011663:Pulmonary Surfactants