Effects of microRNA-155 on interleukin-1 receptor-associated kinase 1 and 4 mRNA expression in liver injury of endotoximia mice

Abstract

Objective To explore the protective effect of microRNA (miRNA)-155 inhibitor on interleukin-1 receptor-associated kinase (IRAK)-1 mRNA and IRAK-4 mRNA in endotoximia induced liver injury in mice. Methods One hundred and twenty male BALB/c mice were randomly divided into healthy control group (n=40), endotoximia group (n=40) and miRNA-155 inhibitor group (n=40). Each group were divided into 6 h, 12 h, 24 h, 48 h subgroups, each of which consisted of 10 mice. The mice in miRNA-155 inhibitor group were administered with miRNA-155 inhibitor[80 mg (kg·d)] via tail vein injection before lipopolysaccharide (LPS) administration while the other two groups treated with normal saline, following 24 hours, model of endotoximia mice was produced by injection of LPS intraperitoneally. At 6 h, 12 h, 24 h, 48 h after LPS exposure, the experimental mice were sacrificed and the liver tissue samples were collected. Histopathological changes, the expression of miRNA-155, IRAK-1 mRNA, IRAK-4 mRNA, tumor necrosis factor (TNF)-α, IL-1, IL-10 were detected. Results LPS exposure resulted in increase of miRNA-155, IRAK-1 mRNA, IRAK-4 mRNA, TNF-α, IL-1 and IL-10 in both endotoximia group and miRNA-155 inhibitor group compared to the control group. miRNA-155 inhibitor resulted in decrease of miRNA-155, IRAK-1 mRNA, IRAK-4 mRNA, TNF-α, IL-1 and IL-10 in miRNA-155 inhibitor group compared to the endotoximia group. There were significant differences of miRNA-155 expression at 12 h, 24 h, 48 h after LPS exposure among 3 groups (P<0.05). Both IRAK-1 mRNA and IRAK-4 mRNA showed significant differences at 12 h, 24 h, 48 h. Turning to inflammation factors, differences were found among 3 groups at all time points (P<0.05). At light-scope, there was improvement in sepsis associated liver injury in miRNA-155 inhibitor group compared to endotoximia group. Conclusion miRNA-155 inhibitor administration appears to down regulate IRAK-1 mRNA and IRAK-4 mRNA expression and further deduce the excessive inflammatory and anti-inflammatory reaction, which may alleviate liver injury in endotoximia mice. Key words: MicroRNA-155; Interleukin-1 receptor-associated kinase mRNA; Interleukin-4 receptor-associated kinase mRNA; Liver injury; Endotoxin; RNA interference; Mice