Treatment with inhaled formulation of angiotensin-(1-7) reverses inflammation and pulmonary remodeling in a model of chronic asthma.

Abstract:

:Asthma is characterized by inflammation, pulmonary remodeling and bronchial hyperresponsiveness. We have previously shown that treatment with angiotensin-(1-7) [Ang-(1-7)] promotes resolution of eosinophilic inflammation and prevents chronic allergic lung inflammation. Here, we evaluated the effect of treatment with the inclusion compound of Ang-(1-7) in hydroxypropyl β-cyclodextrin (HPβCD) given by inhalation on pulmonary remodeling in an ovalbumin (OVA)-induced chronic allergic lung inflammation. Mice were sensitized to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged 3 times per week, for 4 weeks (days 21-46). After the 2nd week of challenge, mice were treated with Ang-(1-7) by inhalation (4.5 μg of Ang-(1-7) included in 6.9 μg of HPβCD for 14 days, i.e. days 35-48). Mice were killed 72 h after the last challenge and blood, bronchoalveolar lavage fluid (BALF) and lungs were collected. Histology and morphometric analysis were performed in the lung. Metalloproteinase (MMP)-9 and MMP-12 expression and activity, IL-5, CCL11 in the lung and plasma IgE were measured. After 2 weeks of OVA challenge there was an increase in plasma IgE and in inflammatory cells infiltration in the lung of asthmatic mice. Treatment with inhaled administration of Ang-(1-7)/HPβCD for 14 days reduced eosinophils, IL5, CCL11 in the lung and plasma IgE. Treatment of asthmatic mice with Ang-(1-7)/HPβCD by inhalation reversed pulmonary remodeling by reducing collagen deposition and MMP-9 and MMP-12 expression and activity. These results show for the first time that treatment by inhalation with Ang-(1-7) can reverse an installed asthma, inhibiting pulmonary inflammation and remodeling.

journal_name

Immunobiology

journal_title

Immunobiology

authors

Magalhães GS,Gregório JF,Ramos KE,Cançado-Ribeiro ATP,Baroni IF,Barcelos LS,Pinho V,Teixeira MM,Santos RAS,Rodrigues-Machado MG,Campagnole-Santos MJ

doi

10.1016/j.imbio.2020.151957

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

151957

issue

3

eissn

0171-2985

issn

1878-3279

pii

S0171-2985(20)30044-9

journal_volume

225

pub_type

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