Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium

Abstract Despite increasing evidence suggesting that angiotensin II type 2 receptor (AT2R) may regulate tissue inflammation, no study has yet analyzed its possible implication in rheumatoid arthritis (RA) synovitis. In this study, we investigated the expression and function of AT2R in synovial tissu...

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Autores principales:	Riccardo Terenzi, Mirko Manetti, Irene Rosa, Eloisa Romano, Felice Galluccio, Serena Guiducci, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42aabc8ad58c42949f9cf7a5099845f7
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spelling	oai:doaj.org-article:42aabc8ad58c42949f9cf7a5099845f72021-12-02T15:05:47ZAngiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium10.1038/s41598-017-13746-w2045-2322https://doaj.org/article/42aabc8ad58c42949f9cf7a5099845f72017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13746-whttps://doaj.org/toc/2045-2322Abstract Despite increasing evidence suggesting that angiotensin II type 2 receptor (AT2R) may regulate tissue inflammation, no study has yet analyzed its possible implication in rheumatoid arthritis (RA) synovitis. In this study, we investigated the expression and function of AT2R in synovial tissue and cultured fibroblast-like synoviocytes (FLS) from RA patients. AT2R expression was strongly increased in RA compared with osteoarthritis (OA) synovium, as well as in in cultured RA-FLS respect to OA-FLS and healthy FLS. Treatment with pro-inflammatory cytokines was able not only to boost AT2R expression in RA-FLS and OA-FLS, but also to induce its de novo expression in healthy FLS. The stimulation of AT2R with the specific agonist CGP42112A significantly reduced gene expression of interleukin (IL)-1β and IL-6 and activation of NF-κB in RA-FLS, while opposite effects were elicited by AT2R small interfering RNA. Moreover, AT2R agonism efficiently decreased RA-FLS proliferation and migration either at baseline or under pro-inflammatory cytokine challenge. In conclusion, AT2R is strongly expressed in key effector cells of rheumatoid synovitis, namely RA-FLS, and the activation of AT2R with a specific agonist may effectively dampen their pro-inflammatory and aggressive behavior. AT2R agonism might represent a novel therapeutic strategy for patients with RA.Riccardo TerenziMirko ManettiIrene RosaEloisa RomanoFelice GalluccioSerena GuiducciLidia Ibba-ManneschiMarco Matucci-CerinicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Riccardo Terenzi Mirko Manetti Irene Rosa Eloisa Romano Felice Galluccio Serena Guiducci Lidia Ibba-Manneschi Marco Matucci-Cerinic Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium
description	Abstract Despite increasing evidence suggesting that angiotensin II type 2 receptor (AT2R) may regulate tissue inflammation, no study has yet analyzed its possible implication in rheumatoid arthritis (RA) synovitis. In this study, we investigated the expression and function of AT2R in synovial tissue and cultured fibroblast-like synoviocytes (FLS) from RA patients. AT2R expression was strongly increased in RA compared with osteoarthritis (OA) synovium, as well as in in cultured RA-FLS respect to OA-FLS and healthy FLS. Treatment with pro-inflammatory cytokines was able not only to boost AT2R expression in RA-FLS and OA-FLS, but also to induce its de novo expression in healthy FLS. The stimulation of AT2R with the specific agonist CGP42112A significantly reduced gene expression of interleukin (IL)-1β and IL-6 and activation of NF-κB in RA-FLS, while opposite effects were elicited by AT2R small interfering RNA. Moreover, AT2R agonism efficiently decreased RA-FLS proliferation and migration either at baseline or under pro-inflammatory cytokine challenge. In conclusion, AT2R is strongly expressed in key effector cells of rheumatoid synovitis, namely RA-FLS, and the activation of AT2R with a specific agonist may effectively dampen their pro-inflammatory and aggressive behavior. AT2R agonism might represent a novel therapeutic strategy for patients with RA.
format	article
author	Riccardo Terenzi Mirko Manetti Irene Rosa Eloisa Romano Felice Galluccio Serena Guiducci Lidia Ibba-Manneschi Marco Matucci-Cerinic
author_facet	Riccardo Terenzi Mirko Manetti Irene Rosa Eloisa Romano Felice Galluccio Serena Guiducci Lidia Ibba-Manneschi Marco Matucci-Cerinic
author_sort	Riccardo Terenzi
title	Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium
title_short	Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium
title_full	Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium
title_fullStr	Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium
title_full_unstemmed	Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium
title_sort	angiotensin ii type 2 receptor (at2r) as a novel modulator of inflammation in rheumatoid arthritis synovium
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/42aabc8ad58c42949f9cf7a5099845f7
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Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium

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