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

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 pa...

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Main 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
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/2401081
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author 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
author_facet 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
author_sort Melissa de Carvalho Santuchi
collection DOAJ
description 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.
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spelling doaj-art-398d3cf411b54a36aacee253ea98e2df2025-02-03T01:31:29ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/24010812401081Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In VivoMelissa de Carvalho Santuchi0Miriane Fernandes Dutra1Juliana Priscila Vago2Kátia Maciel Lima3Izabela Galvão4Fernando Pedro de Souza-Neto5Mario Morais e Silva6Aline Cristina Oliveira7Flávia Carvalho Bittencourt de Oliveira8Ricardo Gonçalves9Mauro Martins Teixeira10Lirlândia Pires Sousa11Robson Augusto Souza dos Santos12Rafaela Fernandes da Silva13Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Clinical and Toxicological Analyses, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Clinical and Toxicological Analyses, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Clinical and Toxicological Analyses, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilThe 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.http://dx.doi.org/10.1155/2019/2401081
spellingShingle 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
Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In Vivo
Mediators of Inflammation
title Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In Vivo
title_full Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In Vivo
title_fullStr Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In Vivo
title_full_unstemmed Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In Vivo
title_short Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In Vivo
title_sort angiotensin 1 7 and alamandine promote anti inflammatory response in macrophages in vitro and in vivo
url http://dx.doi.org/10.1155/2019/2401081
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