title: Ghrelin attenuates lipopolysaccharide-induced acute lung injury through NO pathway.
abstract: BACKGROUND
  In a rat model, ghrelin has been shown to exert an anti-inflammatory effect in cardiovascular disease and arthritis. It also inhibits expression of proinflammatory cytokines. The wide tissue distribution of ghrelin expression and the presence of growth hormone secretagogue receptor (GHS-R) in the lung suggest that ghrelin may be a potential signal modulator in the lung. However, whether ghrelin exerts anti-inflammatory effects on acute lung injury induced by lipopolysaccharide (LPS) remains unknown. Therefore, we sought to investigate the role of ghrelin in LPS-induced acute lung injury and its underlying mechanism.
  
  
  METHODS
  We induced acute lung injury in rats via intratracheal instillation of LPS. We injected ghrelin and Nomega-nitro-L-arginine methyl ester (L-NAME) through the tail vein. Lung injury was assessed by histologic examination 6 hours after injury. Lung macrophages were isolated and incubated with LPS, L-NAME, and ghrelin. Concentrations of TNF-alpha and IL-1beta in bronchoalveolar lavage (BAL) fluid and culture supernatant were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) in BAL fluid and culture supernatant and NO synthase (NOS) in cultured macrophage were detected by a spectrophotometry.
  
  
  RESULTS
  Ghrelin attenuated pulmonary inflammation in LPS-induced acute lung injury, decreased production of proinflammatory cytokines, and increased NO concentrations in BAL fluid. Ghrelin also suppressed LPS-induced expression of proinflammatory cytokines, and increased NOS activity in cultured macrophages and NO concentrations in culture supernatants. The anti-inflammatory effect of ghrelin was inhibited by L-NAME.
  
  
  CONCLUSIONS
  Ghrelin attenuates LPS-induced acute lung inflammation and suppresses LPS-induced proinflammatory cytokine production in lung macrophages, which is partially mediated by increased NO production.
authors.affiliation: West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Shu
authors.forename: Shuangqing
authors.initials: S
authors.lastname: Li
authors.forename: Fengming
authors.initials: F
authors.lastname: Luo
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis; D054439:Ghrelin / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D003470:Culture Media; D016207:Cytokines; D054439:Ghrelin; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase