The Role Of BAFF In LPS-induced Mice Sepsis Model

Objective: To investigate the systemic and organ-specific expression of BAFF in LPSinduced mice sepsis model,as well as the exact role and mechanisms of BAFF in sepsis.Methods: LPS-induced mice sepsis model was established by intraperitoneal injection of LPS into mice.BAFF concentration in the serum,ileum,colon,liver,spleen,kidney and lung of mice was detected by ELISA.To explore the role of BAFF in sepsis mice,mice were administered intraperitoneally with BAFF antibody or control vehicle.Survival rates of sepsis mice were documented in the duration of 72 hours after BAFF antibody administration.The serum concentration of IL-1β,IL-6,TNF-α,IL-10,DAO,D-lactate and FITC-dextran was detected using ELISA.ALT,AST,Cr and LDH were examined to assess organ-specific injury.H&E staining and MPO concentration of ileum were analyzed,and IL-1β,IL-6,TNF-α,IL-10 m RNA expression in the ileum and primary intestinal epithelial cells were examined by RTq PCR,to evaluate the inflammation of small intestine.Western Blot was carried out to detect the expression of tight junction protein(ZO-1,occludin),IκB-α/p-IκB-α,p65/p-p65,MLC/pMLC and MLCK.Results: Compared with control group,systemic and organ-specific BAFF concentration was significantly higher in sepsis mice.Administration of BAFF antibody improved the survival rates of sepsis mice,and down-regulated the expression of IL-1β,IL-6,TNF-α in the serum,ileum and primary intestinal epithelial cells.BAFF antibody also alleviated tissue injury of liver,kidney,myocardium and ileum caused by LPS and reduced the serum concentration of MPO,DAO,D-lactate and FITC-dextran.The protein expression of ZO-1 and occludin were decreased in the ileum of sepsis mice,while p-IκB-α,p-p65,p-MLC and MLCK expression were increased.However,BAFF antibody reversed LPS induced down-regulation of ZO-1 and occludin through NF-κB/MLCK/MLC signaling.Conclusion: BAFF was up-regulated in LPS-induced mice sepsis model.Blockade of BAFF could increase the survival of sepsis mice through alleviation of systemic and organ-specific inflammation and improvement of intestinal barrier function,implying BAFF might be a potential target for sepsis treatment.