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γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury

The mechanisms underlying sepsis-induced cardiomyopathy (SIC) remain poorly understood, and there are no specific therapeutics for SIC. We investigated the effects of maresin conjugates in tissue regeneration 1 (MCTR1) on SIC and explored its potential mechanisms. The experiments were conducted usin...

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Autores principales: Yang, Yi, Li, Xin-Yu, Li, Lin-Chao, Xiao, Ji, Zhu, Yin-Meng, Tian, Yang, Sheng, Yong-Mao, Chen, Yan, Wang, Jian-Guang, Jin, Sheng-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107383/
https://www.ncbi.nlm.nih.gov/pubmed/33981320
http://dx.doi.org/10.3389/fimmu.2021.674542
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author Yang, Yi
Li, Xin-Yu
Li, Lin-Chao
Xiao, Ji
Zhu, Yin-Meng
Tian, Yang
Sheng, Yong-Mao
Chen, Yan
Wang, Jian-Guang
Jin, Sheng-Wei
author_facet Yang, Yi
Li, Xin-Yu
Li, Lin-Chao
Xiao, Ji
Zhu, Yin-Meng
Tian, Yang
Sheng, Yong-Mao
Chen, Yan
Wang, Jian-Guang
Jin, Sheng-Wei
author_sort Yang, Yi
collection PubMed
description The mechanisms underlying sepsis-induced cardiomyopathy (SIC) remain poorly understood, and there are no specific therapeutics for SIC. We investigated the effects of maresin conjugates in tissue regeneration 1 (MCTR1) on SIC and explored its potential mechanisms. The experiments were conducted using an endotoxemia model induced by lipopolysaccharide (LPS). Mice were given MCTR1 intravenously 6 h after LPS stimulation. Echocardiography was performed to assess cardiac function 12 h after LPS administration. Treatment with MCTR1 significantly enhanced cardiac function and reduced LPS-induced increase of mRNA expression levels of inflammation cytokines. Transcriptomic analysis indicated that MCTR1 inhibited neutrophil chemotaxis via the IL-17 signaling pathway. We confirmed that MCTR1 reduced the expressions of neutrophil chemoattractants and neutrophil infiltration in the LPS-stimulated hearts. MCTR1 also resulted in a considerable reduction in IL-17A production mainly derived from γδ T cells. Moreover, our results provided the first evidence that neutralizing IL-17A or depletion of γδ T cells markedly decreased neutrophil recruitment and enhanced cardiac function in LPS-induced cardiac injury. These results suggest that MCTR1 alleviates neutrophil infiltration thereby improves cardiac function in LPS-induced cardiac injury via the IL-17 signaling pathway. Thus, MCTR1 represented a novel therapeutic strategy for patients with SIC.
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spelling pubmed-81073832021-05-11 γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury Yang, Yi Li, Xin-Yu Li, Lin-Chao Xiao, Ji Zhu, Yin-Meng Tian, Yang Sheng, Yong-Mao Chen, Yan Wang, Jian-Guang Jin, Sheng-Wei Front Immunol Immunology The mechanisms underlying sepsis-induced cardiomyopathy (SIC) remain poorly understood, and there are no specific therapeutics for SIC. We investigated the effects of maresin conjugates in tissue regeneration 1 (MCTR1) on SIC and explored its potential mechanisms. The experiments were conducted using an endotoxemia model induced by lipopolysaccharide (LPS). Mice were given MCTR1 intravenously 6 h after LPS stimulation. Echocardiography was performed to assess cardiac function 12 h after LPS administration. Treatment with MCTR1 significantly enhanced cardiac function and reduced LPS-induced increase of mRNA expression levels of inflammation cytokines. Transcriptomic analysis indicated that MCTR1 inhibited neutrophil chemotaxis via the IL-17 signaling pathway. We confirmed that MCTR1 reduced the expressions of neutrophil chemoattractants and neutrophil infiltration in the LPS-stimulated hearts. MCTR1 also resulted in a considerable reduction in IL-17A production mainly derived from γδ T cells. Moreover, our results provided the first evidence that neutralizing IL-17A or depletion of γδ T cells markedly decreased neutrophil recruitment and enhanced cardiac function in LPS-induced cardiac injury. These results suggest that MCTR1 alleviates neutrophil infiltration thereby improves cardiac function in LPS-induced cardiac injury via the IL-17 signaling pathway. Thus, MCTR1 represented a novel therapeutic strategy for patients with SIC. Frontiers Media S.A. 2021-04-26 /pmc/articles/PMC8107383/ /pubmed/33981320 http://dx.doi.org/10.3389/fimmu.2021.674542 Text en Copyright © 2021 Yang, Li, Li, Xiao, Zhu, Tian, Sheng, Chen, Wang and Jin 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
Yang, Yi
Li, Xin-Yu
Li, Lin-Chao
Xiao, Ji
Zhu, Yin-Meng
Tian, Yang
Sheng, Yong-Mao
Chen, Yan
Wang, Jian-Guang
Jin, Sheng-Wei
γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury
title γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury
title_full γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury
title_fullStr γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury
title_full_unstemmed γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury
title_short γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury
title_sort γδ t/interleukin-17a contributes to the effect of maresin conjugates in tissue regeneration 1 on lipopolysaccharide-induced cardiac injury
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107383/
https://www.ncbi.nlm.nih.gov/pubmed/33981320
http://dx.doi.org/10.3389/fimmu.2021.674542
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