Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli

Mounting evidence argues for the significant impact of sex in numerous cardiac pathologies, including myocarditis. Macrophage polarization and activation of cardiac fibroblasts play a key role in myocardial inflammation and remodeling. However, the role of sex in these processes is still poorly unde...

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Autores principales:	Maria Luisa Barcena, Maximilian H. Niehues, Céline Christiansen, Misael Estepa, Natalie Haritonow, Amir H. Sadighi, Ursula Müller-Werdan, Yury Ladilov, Vera Regitz-Zagrosek
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	sex differences inflammation bone marrow macrophages macrophage phenotype activated fibroblasts Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/235fb8ba58fe46c08241f0284585c7b7
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spelling	oai:doaj.org-article:235fb8ba58fe46c08241f0284585c7b72021-11-18T09:21:40ZMale Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli1664-322410.3389/fimmu.2021.758767https://doaj.org/article/235fb8ba58fe46c08241f0284585c7b72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.758767/fullhttps://doaj.org/toc/1664-3224Mounting evidence argues for the significant impact of sex in numerous cardiac pathologies, including myocarditis. Macrophage polarization and activation of cardiac fibroblasts play a key role in myocardial inflammation and remodeling. However, the role of sex in these processes is still poorly understood. In this study, we investigated sex-specific alterations in the polarization of murine bone marrow-derived macrophages (BMMs) and the polarization-related changes in fibroblast activation. Cultured male and female murine BMMs from C57/BL6J mice were polarized into M1 (LPS) and M2 (IL-4/IL-13) macrophages. Furthermore, male and female cardiac fibroblasts from C57/BL6J mice were activated with TNF-α, TGF-β, or conditioned medium from M1 BMMs. We found a significant overexpression of M1 markers (c-fos, NFκB, TNF-α, and IL-1β) and M2 markers (MCP-1 and YM1) in male but not female activated macrophages. In addition, the ROS levels were higher in M1 male BMMs, indicating a stronger polarization. Similarly, the pro-fibrotic markers TGF-β and IL-1β were expressed in activated cardiac male fibroblasts at a significantly higher level than in female fibroblasts. In conclusion, the present study provides strong evidence for the male-specific polarization of BMMs and activation of cardiac fibroblasts in an inflammatory environment. The data show an increased inflammatory response and tissue remodeling in male mice.Maria Luisa BarcenaMaria Luisa BarcenaMaximilian H. NiehuesCéline ChristiansenMisael EstepaMisael EstepaNatalie HaritonowAmir H. SadighiUrsula Müller-WerdanYury LadilovVera Regitz-ZagrosekVera Regitz-ZagrosekFrontiers Media S.A.articlesex differencesinflammationbone marrow macrophagesmacrophage phenotypeactivated fibroblastsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sex differences inflammation bone marrow macrophages macrophage phenotype activated fibroblasts Immunologic diseases. Allergy RC581-607
spellingShingle	sex differences inflammation bone marrow macrophages macrophage phenotype activated fibroblasts Immunologic diseases. Allergy RC581-607 Maria Luisa Barcena Maria Luisa Barcena Maximilian H. Niehues Céline Christiansen Misael Estepa Misael Estepa Natalie Haritonow Amir H. Sadighi Ursula Müller-Werdan Yury Ladilov Vera Regitz-Zagrosek Vera Regitz-Zagrosek Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli
description	Mounting evidence argues for the significant impact of sex in numerous cardiac pathologies, including myocarditis. Macrophage polarization and activation of cardiac fibroblasts play a key role in myocardial inflammation and remodeling. However, the role of sex in these processes is still poorly understood. In this study, we investigated sex-specific alterations in the polarization of murine bone marrow-derived macrophages (BMMs) and the polarization-related changes in fibroblast activation. Cultured male and female murine BMMs from C57/BL6J mice were polarized into M1 (LPS) and M2 (IL-4/IL-13) macrophages. Furthermore, male and female cardiac fibroblasts from C57/BL6J mice were activated with TNF-α, TGF-β, or conditioned medium from M1 BMMs. We found a significant overexpression of M1 markers (c-fos, NFκB, TNF-α, and IL-1β) and M2 markers (MCP-1 and YM1) in male but not female activated macrophages. In addition, the ROS levels were higher in M1 male BMMs, indicating a stronger polarization. Similarly, the pro-fibrotic markers TGF-β and IL-1β were expressed in activated cardiac male fibroblasts at a significantly higher level than in female fibroblasts. In conclusion, the present study provides strong evidence for the male-specific polarization of BMMs and activation of cardiac fibroblasts in an inflammatory environment. The data show an increased inflammatory response and tissue remodeling in male mice.
format	article
author	Maria Luisa Barcena Maria Luisa Barcena Maximilian H. Niehues Céline Christiansen Misael Estepa Misael Estepa Natalie Haritonow Amir H. Sadighi Ursula Müller-Werdan Yury Ladilov Vera Regitz-Zagrosek Vera Regitz-Zagrosek
author_facet	Maria Luisa Barcena Maria Luisa Barcena Maximilian H. Niehues Céline Christiansen Misael Estepa Misael Estepa Natalie Haritonow Amir H. Sadighi Ursula Müller-Werdan Yury Ladilov Vera Regitz-Zagrosek Vera Regitz-Zagrosek
author_sort	Maria Luisa Barcena
title	Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli
title_short	Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli
title_full	Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli
title_fullStr	Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli
title_full_unstemmed	Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli
title_sort	male macrophages and fibroblasts from c57/bl6j mice are more susceptible to inflammatory stimuli
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/235fb8ba58fe46c08241f0284585c7b7
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Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli

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