Protective effects of the SEPS1 gene on lipopolysaccharide-induced sepsis

Abstract

Septic shock and sequential multiple organ failure are the main cause of mortality in patients with sepsis. The induction of inflammation during sepsis is a complex biological cascade, which requires successful therapeutic intervention. Selenoprotein S (SEPS1) is a novel endoplasmic reticulum-resident protein and is important in the production of inflammatory cytokines. The present study attempted to assess the effect of SEPS1 suppression by small interfering RNA (siRNA) on mice with lipopolysaccharide (LPS)-induced sepsis. In total, 30 mice were randomly assigned to three groups: i) H group (LPS-induced sepsis group; n=10): Mice with intraperitoneal injection of LPS (10 mg/kg); ii) K group (scrambled siRNA group; n=10): Mice transfected with scrambled control siRNA 12 h prior to injection with LPS and iii) L group (SEPS1 siRNA group; n=10): Mice transfected with SEPS1 siRNA 12 h prior to injection with LPS. The effects of siRNA were evaluated by SEPS1 gene and protein expression, biochemical parameters including serum alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), lactic dehydrogenase (LDH), creatine kinase (CK) and myocardial kinase (CK-MB), as well as the cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK) was also detected by western blot analysis. In the SEPS1 siRNA group, SEPS1 gene and protein expression decreased significantly, while the levels of TNF-α and IL-6 increased compared with the control group. The biochemical parameters of ALT, AST, BUN, LDH, CK and CK-MB were markedly increased in the SEPS1 siRNA group. The phosphorylation of p38 MAPK was also significantly activated. The decrease in SEPS1 gene and protein expression and the production of TNF-α and IL-6 may correlate with the activation of the p38 MAPK pathway. Biochemical factors and pathological results demonstrated that the damage to vital organs was aggravated. In conclusion, these findings suggested that SEPS1 may protect mice against LPS-induced sepsis and organ damage. Therefore, SEPS1 may be a new target to resolve LPS-induced sepsis.