title: Angiotensin-(1-7) attenuates airway remodelling and hyperresponsiveness in a model of chronic allergic lung inflammation.
abstract: OBJECTIVE
  A long-term imbalance between pro- and anti-inflammatory mediators leads to airway remodelling, which is strongly correlated to most of the symptoms, severity and progression of chronic lung inflammation. The Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis of the renin-angiotensin system is associated with attenuation of acute and chronic inflammatory processes. In this study, we investigated the effects of Ang-(1-7) treatment in a model of chronic allergic lung inflammation.
  
  
  METHODS
  Mice were sensitized to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged three times per week (days 21-46). These mice received Ang-(1-7) (1 μg·h(-1) , s.c.) by osmotic mini-pumps, for the last 28 days. Histology and morphometric analysis were performed in left lung and right ventricle. Airway responsiveness to methacholine, analysis of Ang-(1-7) levels (RIA), collagen I and III (qRT-PCR), ERK1/2 and JNK (Western blotting), IgE (elisa), cytokines and chemokines (elisa multiplex), and immunohistochemistry for Mas receptors were performed.
  
  
  RESULTS
  Infusion of Ang-(1-7) in OVA-sensitized and challenged mice decreased inflammatory cell infiltration and collagen deposition in the airways and lung parenchyma, and prevented bronchial hyperresponsiveness. These effects were accompanied by decreased IgE and ERK1/2 phosphorylation, and decreased pro-inflammatory cytokines. Mas receptors were detected in the epithelium and bronchial smooth muscle, suggesting a site in the lung for the beneficial actions of Ang-(1-7).
  
  
  CONCLUSIONS
  Ang-(1-7) exerted beneficial attenuation of three major features of chronic asthma: lung inflammation, airway remodelling and hyperresponsiveness. Our results support an important protective role of Ang-(1-7) in lung inflammation.
authors.affiliation: Department of Physiology and Biophysics, National Institute of Science and Technology in Nanobiopharmaceutics (INCT-NANOBIOFAR), Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: G S
authors.initials: GS
authors.lastname: Magalhães
authors.forename: M G
authors.initials: MG
authors.lastname: Rodrigues-Machado
authors.forename: D
authors.initials: D
authors.lastname: Motta-Santos
authors.forename: A R
authors.initials: AR
authors.lastname: Silva
authors.forename: M V
authors.initials: MV
authors.lastname: Caliari
authors.forename: L O
authors.initials: LO
authors.lastname: Prata
authors.forename: S C
authors.initials: SC
authors.lastname: Abreu
authors.forename: P R M
authors.initials: PR
authors.lastname: Rocco
authors.forename: L S
authors.initials: LS
authors.lastname: Barcelos
authors.forename: R A S
authors.initials: RA
authors.lastname: Santos
authors.forename: M J
authors.initials: MJ
authors.lastname: Campagnole-Santos
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D007073:Immunoglobulin E / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010047:Ovalbumin; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D007073:Immunoglobulin E; D010047:Ovalbumin; D003094:Collagen; D000803:Angiotensin I; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C118790:angiotensin I (1-7)