title: Ghrelin ameliorates bleomycin-induced acute lung injury by protecting alveolar epithelial cells and suppressing lung inflammation.
abstract: Acute lung injury is a critical illness syndrome consisting of acute respiratory failure with bilateral pulmonary infiltrates that is refractory to current therapies. Acute lung injury is characterized by injury of the alveolar capillary barrier, neutrophil accumulation, and induction of pro-inflammatory cytokines followed by devastating lung fibrosis. Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation, and promotes cell survival. We investigated the pharmacological potential of ghrelin in the treatment of acute lung injury by using a bleomycin-induced acute lung injury model in mice. Ghrelin or saline was given to mice daily starting 1 day after bleomycin administration. Ghrelin-treated mice showed a definitively higher survival rate than saline-treated ones. They also had smaller reductions in body weight and food intake. The amelioration of neutrophil alveolar infiltration, pulmonary vascular permeability, induction of pro-inflammatory cytokines, and subsequent lung fibrosis were notable in ghrelin-treated mice. Additionally, ghrelin administration reduced the injury-induced apoptosis of alveolar epithelial cells. Our results indicate that ghrelin administration exerts a protective effect against acute lung injury by protecting the alveolar epithelial cells and regulating lung inflammation, and highlight ghrelin as a promising therapeutic agent for the management of this intractable disease.
authors: Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors: Yoshifumi
authors: Y
authors: Imazu
authors: Shigehisa
authors: S
authors: Yanagi
authors: Kahori
authors: K
authors: Miyoshi
authors: Hironobu
authors: H
authors: Tsubouchi
authors: Shu-Ichi
authors: S
authors: Yamashita
authors: Nobuhiro
authors: N
authors: Matsumoto
authors: Jun-Ichi
authors: J
authors: Ashitani
authors: Kenji
authors: K
authors: Kangawa
authors: Masamitsu
authors: M
authors: Nakazato
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D007267:Injections; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000150:complications / Q000188:drug therapy
chemical_list: D016207:Cytokines; D054439:Ghrelin; D001761:Bleomycin