Frontiers in Cardiovascular Medicine (Sep 2022)

IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice

  • 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

DOI
https://doi.org/10.3389/fcvm.2022.950029
Journal volume & issue
Vol. 9

Abstract

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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.

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