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IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice
BACKGROUND: Cardiac dysfunction is one of the most common complications of sepsis and is associated with the adverse outcomes and high mortality of sepsis patients. IL-12p40, the common subunit of IL-12 and IL-23, has been shown to be involved in a variety of inflammation-related diseases, such as p...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9523082/ https://www.ncbi.nlm.nih.gov/pubmed/36186987 http://dx.doi.org/10.3389/fcvm.2022.950029 |
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author | Liu, Menglin Wang, Zhen Zhang, Jishou Ye, Di Wang, Menglong Xu, Yao Zhao, Mengmeng Feng, Yongqi Lu, Xiyi Pan, Heng Pan, Wei Wei, Cheng Tian, Dan Li, Wenqiang Lyu, Jingjun Ye, Jing Wan, Jun |
author_facet | Liu, Menglin Wang, Zhen Zhang, Jishou Ye, Di Wang, Menglong Xu, Yao Zhao, Mengmeng Feng, Yongqi Lu, Xiyi Pan, Heng Pan, Wei Wei, Cheng Tian, Dan Li, Wenqiang Lyu, Jingjun Ye, Jing Wan, Jun |
author_sort | Liu, Menglin |
collection | PubMed |
description | BACKGROUND: Cardiac dysfunction is one of the most common complications of sepsis and is associated with the adverse outcomes and high mortality of sepsis patients. IL-12p40, the common subunit of IL-12 and IL-23, has been shown to be involved in a variety of inflammation-related diseases, such as psoriasis and inflammatory bowel disease. However, the role of IL-12p40 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains obscure. This study aimed to explore the role of IL-12p40 in LPS-induced cardiac dysfunction and its potential mechanisms. METHODS: In this study, mice were treated with LPS and the cardiac expression of IL-12p40 was determined. Then, IL-12p40(–/–) mice were used to detect the role and mechanisms of IL-12p40 in LPS-induced cardiac injury. In addition, monocytes were adoptively transferred to IL-12p40(–/–) mice to explore their effects on LPS-induced cardiac dysfunction. RESULTS: The results showed that cardiac IL-12p40 expression was significantly increased after treated with LPS. In addition, IL-12p40 deletion significantly aggravated LPS-induced cardiac dysfunction, evidenced by the increased serum levels of cardiomyocyte injury markers and heart injury scores, as well as by the deteriorated cardiac function. Moreover, IL-12p40 deletion increased LPS-induced monocyte accumulation and cardiac expression of inflammatory cytokines, as well as enhanced the activation of the NF-κB and MAPK pathways. Furthermore, adoptive transfer WT mouse monocytes to IL-12p40(−/−) mice alleviated LPS-induced cardiac dysfunction and decreased the phosphorylation of p65. CONCLUSION: IL-12p40 deletion significantly aggravated LPS-induced cardiac injury and cardiac dysfunction in mice by regulating the NF-κB and MAPK signaling pathways, and this process was related to monocytes. Therefore, IL-12p40 show a protective role in SIC, and IL-12p40 deficiency or anti-IL-12p40 monoclonal antibodies may be detrimental to patients with SIC. |
format | Online Article Text |
id | pubmed-9523082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95230822022-10-01 IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice Liu, Menglin Wang, Zhen Zhang, Jishou Ye, Di Wang, Menglong Xu, Yao Zhao, Mengmeng Feng, Yongqi Lu, Xiyi Pan, Heng Pan, Wei Wei, Cheng Tian, Dan Li, Wenqiang Lyu, Jingjun Ye, Jing Wan, Jun Front Cardiovasc Med Cardiovascular Medicine BACKGROUND: Cardiac dysfunction is one of the most common complications of sepsis and is associated with the adverse outcomes and high mortality of sepsis patients. IL-12p40, the common subunit of IL-12 and IL-23, has been shown to be involved in a variety of inflammation-related diseases, such as psoriasis and inflammatory bowel disease. However, the role of IL-12p40 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains obscure. This study aimed to explore the role of IL-12p40 in LPS-induced cardiac dysfunction and its potential mechanisms. METHODS: In this study, mice were treated with LPS and the cardiac expression of IL-12p40 was determined. Then, IL-12p40(–/–) mice were used to detect the role and mechanisms of IL-12p40 in LPS-induced cardiac injury. In addition, monocytes were adoptively transferred to IL-12p40(–/–) mice to explore their effects on LPS-induced cardiac dysfunction. RESULTS: The results showed that cardiac IL-12p40 expression was significantly increased after treated with LPS. In addition, IL-12p40 deletion significantly aggravated LPS-induced cardiac dysfunction, evidenced by the increased serum levels of cardiomyocyte injury markers and heart injury scores, as well as by the deteriorated cardiac function. Moreover, IL-12p40 deletion increased LPS-induced monocyte accumulation and cardiac expression of inflammatory cytokines, as well as enhanced the activation of the NF-κB and MAPK pathways. Furthermore, adoptive transfer WT mouse monocytes to IL-12p40(−/−) mice alleviated LPS-induced cardiac dysfunction and decreased the phosphorylation of p65. CONCLUSION: IL-12p40 deletion significantly aggravated LPS-induced cardiac injury and cardiac dysfunction in mice by regulating the NF-κB and MAPK signaling pathways, and this process was related to monocytes. Therefore, IL-12p40 show a protective role in SIC, and IL-12p40 deficiency or anti-IL-12p40 monoclonal antibodies may be detrimental to patients with SIC. Frontiers Media S.A. 2022-09-16 /pmc/articles/PMC9523082/ /pubmed/36186987 http://dx.doi.org/10.3389/fcvm.2022.950029 Text en Copyright © 2022 Liu, Wang, Zhang, Ye, Wang, Xu, Zhao, Feng, Lu, Pan, Pan, Wei, Tian, Li, Lyu, Ye and Wan. 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 | Cardiovascular Medicine Liu, Menglin Wang, Zhen Zhang, Jishou Ye, Di Wang, Menglong Xu, Yao Zhao, Mengmeng Feng, Yongqi Lu, Xiyi Pan, Heng Pan, Wei Wei, Cheng Tian, Dan Li, Wenqiang Lyu, Jingjun Ye, Jing Wan, Jun IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice |
title | IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice |
title_full | IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice |
title_fullStr | IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice |
title_full_unstemmed | IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice |
title_short | IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice |
title_sort | il-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9523082/ https://www.ncbi.nlm.nih.gov/pubmed/36186987 http://dx.doi.org/10.3389/fcvm.2022.950029 |
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