GSTP1 inhibits inflammasome activation of astrocytes in the hippocampus of epileptic rats through regulation of the JNK pathway / 中风与神经疾病杂志

ABSTRACT

@#Objective To investigate the effects and related molecular mechanisms of glutathione S-transferase pi 1 (GSTP1) on the inflammasome activation of astrocytes.Methods A model of epilepsy was established in 10-week-old male SD rats by intraperitoneal injection of lithium chloride (n=8),and brain tissues were collected from the hippocampus.Rat primary astrocytes were treated with different concentrations of lipopolysaccharide (0 μg/ml,0.1 μg/ml,1 μg/ml,10 μg/ml and 100 μg/ml) for 48 h.The protein levels of GSTP1,JNK and p-JNK in tissues and cells were measured by Western blotting.The levels of TNF-α,IL-1β,IL-6 were detected by enzyme-linked immunosorbent assay.The levels of glutamate (Glu) were detected by high pressure liquid chromatography.The lipopolysaccharide-induced astrocytes were transiently transfected with GSTP1 overexpression vector and were treated with Anisomycin (JNK activator),and the inflammatory activation of astrocytes was observed.Results The protein levels of GSTP1 were lower in the hippocampal brain tissues of epileptic rats than those in normal rats,while the protein levels of p-JNK and the levels of TNF-α,IL-1β,IL-6 and Glu were higher in epileptic rats than those in normal rats (P<0.05).GSTP1 was negatively correlated with p-JNK protein expression level (P<0.05).Lipopolysaccharide-induced inflammasome activation in astrocytes,as evidenced by a dose-dependent decrease in the protein expression levels of GSTP1 and a dose-dependent increase in the protein levels of p-JNK and the levels of TNF-α,IL-1β,IL-6 and Glu (P<0.05).Overexpression of GSTP1 inhibited lipopolysaccharide-induced inflammasome activation of astrocytes,while Anisomycin partially reversed the inhibitory effect of GSTP1. Conclusion GSTP1 inhibits inflammasome activation of astrocytes in the hippocampus of epileptic rats,and its molecular mechanism is related to JNK pathway inhibition.