title: Adrenomedullin in inflammatory process associated with experimental pulmonary fibrosis.
abstract: BACKGROUND
  Adrenomedullin (AM), a 52-amino acid ringed-structure peptide with C-terminal amidation, was originally isolated from human pheochromocytoma. AM are widely distributed in various tissues and acts as a local vasoactive hormone in various conditions.
  
  
  METHODS
  In the present study, we investigated the efficacy of AM on the animal model of bleomycin (BLM)-induced lung injury. Mice were subjected to intratracheal administration of BLM and were assigned to receive AM daily by an intraperitoneal injection of 200 ngr/kg.
  
  
  CONCLUSIONS
  Myeloperoxidase activity, lung histology, immunohistochemical analyses for cytokines and adhesion molecules expression, inducible nitric oxide synthase (iNOS), nitrotyrosine, and poly (ADP-ribose) polymerase (PARP) were performed one week after fibrosis induction. Lung histology and transforming growth factor beta (TGF-β) were performed 14 and 21 days after treatments. After bleomycin administration, AM-treated mice exhibited a reduced degree of lung damage and inflammation compared with BLM-treated mice, as shown by the reduction of (1) myeloperoxidase activity (MPO), (2) cytokines and adhesion molecules expression, (3) nitric oxide synthase expression, (4) the nitration of tyrosine residues, (5) poly (ADP-ribose) (PAR) formation, a product of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) (6) transforming growth factor beta (TGF-β) (7)and the degree of lung injury.
  
  
  CONCLUSIONS
  Our results indicate that AM administration is able to prevent bleomycin induced lung injury through the down regulation of proinflammatory factors.
authors.affiliation: IRCCS Centro Neurolesi Bonino-Pulejo, S,S, 113 Via Palermo, CTR Casazza, Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Elena
authors.initials: E
authors.lastname: Talero
authors.forename: Maria
authors.initials: M
authors.lastname: Galuppo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Virginia
authors.initials: V
authors.lastname: Motilva
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D053607:Adrenomedullin / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001761:Bleomycin; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018836:Inflammation Mediators; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D053607:Adrenomedullin; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011065:Poly(ADP-ribose) Polymerases