Interleukin-18 gene deletion protects against sepsis-induced cardiac dysfunction by inhibiting PP2A activity

International Journal of Cardiology
Yoshitaka OkuharaShinichi Hirotani

Abstract

Interleukin-18 (IL-18) neutralization protects against lipopolysaccharide (LPS)-induced injuries, including myocardial dysfunction. However, the mechanism is yet to be fully elucidated. The aim of the present study was to determine whether IL-18 gene deletion prevents sepsis-induced cardiac dysfunction and to elucidate the potential mechanisms underlying IL-18-mediated cardiotoxicity by LPS. Ten-week-old male wild-type (WT) and IL-18 knockout (IL-18 KO) mice were intraperitoneally administered LPS. Serial echocardiography showed better systolic pump function and less left ventricular (LV) dilatation in LPS-treated IL-18 KO mice compared with those in LPS-treated WT mice. LPS treatment significantly decreased the levels of phospholamban (PLN) and Akt phosphorylation in WT mice compared with those in saline-treated WT mice, while the LPS-induced decrease in the phosphorylation levels was attenuated in IL-18 KO mice compared with that in WT mice. IL-18 gene deletion also attenuated an LPS-induced increase of type 2 protein phosphatase 2A (PP2A) activity, a molecule that dephosphorylates PLN and Akt. There was no difference in type 1 protein phosphatase (PP1) activity. To address whether IL-18 affects PLN and Akt phosphorylation vi...Continue Reading

Citations

May 31, 2018·Current Opinion in Critical Care·Keith R Walley
Mar 8, 2019·FEMS Microbiology Reviews·Tomasz Skirecki, Jean-Marc Cavaillon
Feb 6, 2020·Experimental and Therapeutic Medicine·Meirong ZhuShaoqin Wang
Aug 15, 2020·Journal of Cellular Physiology·Alessandra VecchiéAntonio Abbate
Apr 22, 2020·Heart Failure Reviews·Zheng MaJiu-Chang Zhong

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