British journal of pharmacology, 2015-05, Vol.172 (9), p.2330-2342
2015
Details
- Autor(en) / Beteiligte
- Titel
- Angiotensin‐(1‐7) attenuates airway remodelling and hyperresponsiveness in a model of chronic allergic lung inflammation
- Ist Teil von
- British journal of pharmacology, 2015-05, Vol.172 (9), p.2330-2342
- Ort / Verlag
- England: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2015
- Link zum Volltext
- Quelle
- Wiley-Blackwell Full Collection
- Beschreibungen/Notizen
- 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 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. 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 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. Key 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 and Implications 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0007-1188eISSN: 1476-5381DOI: 10.1111/bph.13057Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4403097
- Format
- –
- Schlagworte
- Airway Remodeling - drug effects, Angiotensin I - pharmacology, Animals, Anti-Inflammatory Agents - pharmacology, Bronchial Hyperreactivity - chemically induced, Bronchial Hyperreactivity - metabolism, Bronchial Hyperreactivity - physiopathology, Bronchial Hyperreactivity - prevention & control, Bronchoconstriction - drug effects, Collagen - metabolism, Cytokines - metabolism, Disease Models, Animal, Hypertrophy, Right Ventricular - chemically induced, Hypertrophy, Right Ventricular - physiopathology, Hypertrophy, Right Ventricular - prevention & control, Immunoglobulin E - blood, Inflammation Mediators - metabolism, Lung - drug effects, Lung - metabolism, Lung - physiopathology, Male, Mice, Inbred BALB C, Mitogen-Activated Protein Kinase 1 - metabolism, Mitogen-Activated Protein Kinase 3 - metabolism, Ovalbumin, Peptide Fragments - pharmacology, Phosphorylation, Pneumonia - chemically induced, Pneumonia - metabolism, Pneumonia - physiopathology, Pneumonia - prevention & control, Proto-Oncogene Proteins - agonists, Proto-Oncogene Proteins - metabolism, Receptors, G-Protein-Coupled - agonists, Receptors, G-Protein-Coupled - metabolism, Research Papers, Respiratory Hypersensitivity - chemically induced, Respiratory Hypersensitivity - metabolism, Respiratory Hypersensitivity - physiopathology, Respiratory Hypersensitivity - prevention & control, Signal Transduction - drug effects