IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice
BackgroundCardiac 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 pso...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.950029/full |
| _version_ | 1811183554086830080 |
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| author | Menglin Liu Zhen Wang Jishou Zhang Di Ye Menglong Wang Yao Xu Mengmeng Zhao Yongqi Feng Xiyi Lu Heng Pan Wei Pan Cheng Wei Dan Tian Wenqiang Li Jingjun Lyu Jing Ye Jun Wan |
| author_facet | Menglin Liu Zhen Wang Jishou Zhang Di Ye Menglong Wang Yao Xu Mengmeng Zhao Yongqi Feng Xiyi Lu Heng Pan Wei Pan Cheng Wei Dan Tian Wenqiang Li Jingjun Lyu Jing Ye Jun Wan |
| author_sort | Menglin Liu |
| collection | DOAJ |
| description | BackgroundCardiac 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.MethodsIn 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.ResultsThe 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.ConclusionIL-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. |
| first_indexed | 2024-04-11T09:48:42Z |
| format | Article |
| id | doaj.art-79f9b33812fb425ca5a03badc1cb05d0 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-11T09:48:42Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-79f9b33812fb425ca5a03badc1cb05d02022-12-22T04:30:53ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-09-01910.3389/fcvm.2022.950029950029IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in miceMenglin Liu0Zhen Wang1Jishou Zhang2Di Ye3Menglong Wang4Yao Xu5Mengmeng Zhao6Yongqi Feng7Xiyi Lu8Heng Pan9Wei Pan10Cheng Wei11Dan Tian12Wenqiang Li13Jingjun Lyu14Jing Ye15Jun Wan16Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Emergency, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Emergency, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Emergency, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaBackgroundCardiac 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.MethodsIn 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.ResultsThe 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.ConclusionIL-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.https://www.frontiersin.org/articles/10.3389/fcvm.2022.950029/fullsepsisIL-12p40 deletioncardiac dysfunctionmonocytesLPS |
| spellingShingle | Menglin Liu Zhen Wang Jishou Zhang Di Ye Menglong Wang Yao Xu Mengmeng Zhao Yongqi Feng Xiyi Lu Heng Pan Wei Pan Cheng Wei Dan Tian Wenqiang Li Jingjun Lyu Jing Ye Jun Wan IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice Frontiers in Cardiovascular Medicine sepsis IL-12p40 deletion cardiac dysfunction monocytes LPS |
| 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 | sepsis IL-12p40 deletion cardiac dysfunction monocytes LPS |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.950029/full |
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