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Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In Vivo

Authors :
Melissa de Carvalho Santuchi
Miriane Fernandes Dutra
Juliana Priscila Vago
Kátia Maciel Lima
Izabela Galvão
Fernando Pedro de Souza-Neto
Mario Morais e Silva
Aline Cristina Oliveira
Flávia Carvalho Bittencourt de Oliveira
Ricardo Gonçalves
Mauro Martins Teixeira
Lirlândia Pires Sousa
Robson Augusto Souza dos Santos
Rafaela Fernandes da Silva
Source :
Mediators of Inflammation, Vol 2019 (2019)
Publication Year :
2019
Publisher :
Hindawi Limited, 2019.

Abstract

The renin-angiotensin system (RAS) peptides play an important role in inflammation. Resolution of inflammation contributes to restore tissue homeostasis, and it is characterized by neutrophil apoptosis and their subsequent removal by macrophages, which are remarkable plastic cells involved in the pathophysiology of diverse inflammatory diseases. However, the effects of RAS peptides on different macrophage phenotypes are still emerging. Here, we evaluated the effects of angiotensin-(1-7) (Ang-(1-7)) and the most novel RAS peptide, alamandine, on resting (M0), proinflammatory M(LPS+IFN-γ), and anti-inflammatory M(IL-4) macrophage phenotypes in vitro, as well as on specific immune cell populations and macrophage subsets into the pleural cavity of LPS-induced pleurisy in mice. Our results showed that Ang-(1-7) and alamandine, through Mas and MrgD receptors, respectively, do not affect M0 macrophages but reduce the proinflammatory TNF-α, CCL2, and IL-1β transcript expression levels in LPS+IFN-γ-stimulated macrophages. Therapeutic administration of these peptides in LPS-induced inflammation in mice decreased the number of neutrophils and M1 (F4/80lowGr1+CD11bmed) macrophage frequency without affecting the other investigated macrophage subsets. Our data suggested that both Ang-(1-7) and alamandine, through their respective receptors Mas and MrgD, promote an anti-inflammatory reprogramming of M(LPS+IFN-γ)/M1 macrophages under inflammatory circumstances and potentiate the reprogramming induced by IL-4. In conclusion, our work sheds light on the emerging proresolving properties of Ang-(1-7) and alamandine, opening new avenues for the treatment of inflammatory diseases.

Subjects

Subjects :
Pathology
RB1-214

Details

Language :
English
ISSN :
09629351 and 14661861
Volume :
2019
Database :
Directory of Open Access Journals
Journal :
Mediators of Inflammation
Publication Type :
Academic Journal
Accession number :
edsdoj.398d3cf411b54a36aacee253ea98e2df
Document Type :
article
Full Text :
https://doi.org/10.1155/2019/2401081