Selenomethionine modulates the JAK2 / STAT3 / A20 pathway through oxidative stress to alleviate LPS-induced pyroptosis and inflammation in chicken hearts

Abstract

Selenium (Se) is involved in many physiopathologic processes in humans and animals and is strongly associated with the development of heart disease. Lipopolysaccharides (LPS) are cell wall components of gram-negative bacteria that are present in large quantities during environmental pollution. To investigate the mechanism of LPS-induced cardiac injury and the efficacy of the therapeutic effect of SeMet on LPS, a chicken model supplemented with selenomethionine (SeMet) and/or LPS treatment, as well as a primary chicken embryo cardiomyocyte model with the combined effect of SeMet / JAK2 inhibitor (INCB018424) and/or LPS were established in this experiment. CCK8 kit, Trypan blue staining, DCFH-DA staining, oxidative stress kits, immunofluorescence staining, LDH kit, real-time fluorescence quantitative PCR, and western blot were used. The results proved that LPS exposure led to ROS explosion, hindered the antioxidant system, promoted the expression of the JAK2 pathway, and increased the expression of genes involved in the pyroptosis pathway, inflammatory factors, and heat shock proteins (HSPs). Upon co-treatment with SeMet and LPS, SeMet reduced LPS-induced pyroptosis and inflammation and restored the expression of HSPs by inhibiting the ROS burst and modulating the antioxidant capacity. Co-treatment with INCB018424 and LPS resulted in inhibited of the JAK2 pathway, attenuating pyroptosis, inflammation, and high expression of HSPs. Thus, LPS induced pyroptosis, inflammation, and changes in HSPs activity by activating of the JAK2 / STAT3 / A20 signaling axis in chicken hearts. Moreover, SeMet has a positive effect on LPS-induced injury. This work further provides a theoretical basis for treating cardiac injury by SeMet.