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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: Barcena, Maria Luisa, Niehues, Maximilian H., Christiansen, Céline, Estepa, Misael, Haritonow, Natalie, Sadighi, Amir H., Müller-Werdan, Ursula, Ladilov, Yury, Regitz-Zagrosek, Vera
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637417/
https://www.ncbi.nlm.nih.gov/pubmed/34867999
http://dx.doi.org/10.3389/fimmu.2021.758767
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author Barcena, Maria Luisa
Niehues, Maximilian H.
Christiansen, Céline
Estepa, Misael
Haritonow, Natalie
Sadighi, Amir H.
Müller-Werdan, Ursula
Ladilov, Yury
Regitz-Zagrosek, Vera
author_facet Barcena, Maria Luisa
Niehues, Maximilian H.
Christiansen, Céline
Estepa, Misael
Haritonow, Natalie
Sadighi, Amir H.
Müller-Werdan, Ursula
Ladilov, Yury
Regitz-Zagrosek, Vera
author_sort Barcena, Maria Luisa
collection PubMed
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.
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spelling pubmed-86374172021-12-03 Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli Barcena, Maria Luisa Niehues, Maximilian H. Christiansen, Céline Estepa, Misael Haritonow, Natalie Sadighi, Amir H. Müller-Werdan, Ursula Ladilov, Yury Regitz-Zagrosek, Vera Front Immunol Immunology 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. Frontiers Media S.A. 2021-11-18 /pmc/articles/PMC8637417/ /pubmed/34867999 http://dx.doi.org/10.3389/fimmu.2021.758767 Text en Copyright © 2021 Barcena, Niehues, Christiansen, Estepa, Haritonow, Sadighi, Müller-Werdan, Ladilov and Regitz-Zagrosek https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Barcena, Maria Luisa
Niehues, Maximilian H.
Christiansen, Céline
Estepa, Misael
Haritonow, Natalie
Sadighi, Amir H.
Müller-Werdan, Ursula
Ladilov, Yury
Regitz-Zagrosek, Vera
Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli
title 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_short 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
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637417/
https://www.ncbi.nlm.nih.gov/pubmed/34867999
http://dx.doi.org/10.3389/fimmu.2021.758767
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