Chronic allergic pulmonary inflammation is aggravated in angiotensin-(1-7) Mas receptor knockout mice

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Item Type:	Article
Title:	Chronic allergic pulmonary inflammation is aggravated in angiotensin-(1-7) Mas receptor knockout mice
Creators Name:	Magalhaes, G.S., Rodrigues-Machado, M.G., Motta-Santos, D., Alenina, N., Bader, M., Santos, R.A.S., Barcelos, L.S. and Campagnole-Santos, M.J.
Abstract:	Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor pathway is currently recognized as a counterbalancing mechanism of the renin-angiotensin system in different pathophysiological conditions. We have previously described that treatment with Ang-(1-7) attenuates lung inflammation and remodeling in an experimental model of asthma. In the present study, we investigated whether lack of Mas receptor could alter the inflammatory response in a model of chronic allergic lung inflammation induced by ovalbumin (OVA). MasWT and MasKO mice were subjected to 4 doses of OVA (20microg/mice, i.p.) with 14 days interval. At the 21st day, nebulization with OVA (1%) was started, 3 times/week until the 46th day. Control groups received saline (0.9%, i.p.) and were nebulized with saline (0.9%). MasWT-OVA developed a modest inflammatory response and minor pulmonary remodeling to OVA challenge. Strikingly, MasKO-OVA presented a significant increase in inflammatory cell infiltrate, extracellular matrix deposition, increase in thickening of the alveolar parenchyma, increase in thickening of the smooth muscle layer of the pulmonary arterioles, increase in pro-inflammatory cytokine and chemokines levels in the lungs, characteristic of chronic asthma. Additionally, MasKO-OVA presented an increase in ERK1/2 phosphorylation in comparison to MasWT-OVA. Furthermore, MasKO-OVA showed a worst performance in a test of maximum physical exercise in comparison to MasWT-OVA. Our study shows that effects triggered by Mas receptor are important to attenuate the inflammatory and remodeling processes in a model of allergic lung inflammation in mice. Our data indicate that impairment of Ang-(1-7)/Mas receptor pathway may lead to worsening of the pathophysiological changes of asthma.
Keywords:	Asthma, Airway Remodeling, Pulmonary Remodeling, Mas Receptor and Angiotensin-(1-7), Animals, Mice
Source:	American Journal of Physiology Lung Cellular and Molecular Physiology
ISSN:	1040-0605
Publisher:	American Physiological Society
Volume:	311
Number:	6
Page Range:	L1141-L1148
Date:	12 December 2016
Official Publication:	https://doi.org/10.1152/ajplung.00029.2016
PubMed:	View item in PubMed

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