Premium
A ngiotensin‐(1‐7) attenuates airway remodelling and hyperresponsiveness in a model of chronic allergic lung inflammation
Author(s) -
Magalhães G S,
RodriguesMachado M G,
MottaSantos D,
Silva A R,
Caliari M V,
Prata L O,
Abreu S C,
Rocco P R M,
Barcelos L S,
Santos R A S,
CampagnoleSantos M J
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13057
Subject(s) - ovalbumin , medicine , methacholine , lung , inflammation , immunology , receptor , endocrinology , immunoglobulin e , pathology , immune system , respiratory disease , antibody
Background and Purpose 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 A ngiotensin‐(1‐7) [ A ng‐(1‐7)]/ M as 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 A ng‐(1‐7) treatment in a model of chronic allergic lung inflammation. Experimental Approach 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 A ng‐(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 A ng‐(1‐7) levels ( RIA ), collagen I and III ( qRT ‐ PCR ), ERK 1/2 and JNK ( W estern blotting), IgE ( elisa ), cytokines and chemokines ( elisa multiplex), and immunohistochemistry for M as receptors were performed. Key Results Infusion of A ng‐(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 ERK 1/2 phosphorylation, and decreased pro‐inflammatory cytokines. M as receptors were detected in the epithelium and bronchial smooth muscle, suggesting a site in the lung for the beneficial actions of A ng‐(1‐7). Conclusions and Implications A ng‐(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.