IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis
Mengmeng Zhao,
Zihui Zheng,
Pingan Zhang,
Yao Xu,
Jishou Zhang,
Shanshan Peng,
Jianfang Liu,
Wei Pan,
Zheng Yin,
Shuwan Xu,
Cheng Wei,
Jun Wan,
Menglong Wang
Affiliations
Mengmeng Zhao
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Zihui Zheng
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Pingan Zhang
Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, P.R. China
Yao Xu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Jishou Zhang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Shanshan Peng
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Jianfang Liu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Wei Pan
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Zheng Yin
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Shuwan Xu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Cheng Wei
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China
Jun Wan
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China; Corresponding author
Menglong Wang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China; Corresponding author
Summary: Cardiac dysfunction is a well-recognized complication of sepsis and seriously affects the prognosis of sepsis patients. IL-30 has been reported to exert anti-inflammatory effects in various diseases. However, the role of IL-30 in sepsis-induced myocardial dysfunction (SIMD) remains unclear. Here, we explored the protective role of IL-30 in cecum ligation and puncture (CLP)-induced SIMD mice. IL-30 expression increased in the cardiac tissues of septic mice and was mainly derived from macrophages. IL-30 deletion or neutralization aggravated sepsis-induced cardiac dysfunction and injury, whereas recombinant IL-30 treatment significantly ameliorated it. Mechanistically, IL-30 deficiency exerts pro-inflammatory effects by promoting Ly6Chigh macrophage polarization and pyroptosis. Inhibiting NLRP3 with MCC950 significantly reversed cardiac dysfunction, macrophage polarization and pyroptosis aggravated by IL-30 deficiency. Recombinant IL-30 inhibited pro-inflammatory macrophage polarization and pyroptosis in vivo and vitro. Taken together, these results suggest that IL-30 protects against SIMD by inhibiting pro-inflammatory macrophage polarization and pyroptosis.
