Role of p38MAPK in production of pro-inflammatory cytokines in Kupffer cells from severe acute pancreatitis rats / 中国病理生理杂志

ABSTRACT

AIM: To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway in the Kupffer cells (KCs) production of pro-inflammatory cytokines, tumor necrosis factor-?(TNF-?) and interleukin-1?(IL-1?), in severe acute pancreatitis (SAP) rats. METHODS: Sprague-Dwaley rats were randomized into three groups ①sham operation rats, ②SAP rats, ③SAP rats given the p38 MAPK inhibitor CNI-1493(10 mg/kg, iv). The SAP model was induced by the bili-pancreatic duct infusion with 5% sterile soduim taurocholate solution. Rats from each group were killed at 12 h after sham operation or SAP and Kupffer cells (KCs) were isolated. The mRNA expressions of TNF-? and IL-1? (by quantitative real-time RT-PCR) and p38 MAPK activity (by Western blot analysis) in KCs were examined. The levels of TNF-? and IL-1? in plasma were determined by ELISA. RESULTS: There was a significant acvitation of p38 MAPK in KCs harvested from SAP rats than those from sham operation rats. SAP also promoted the mRNA expressions of TNF-? and IL-1? in KCs and the plasma levels of TNF-? and IL-1?. These events were significantly inhibited by treatment with CNI-1493.CONCLUSIONS: p38 MAPK activation is one important aspect of the signaling events that may mediate the KCs production of pro-inflammatory cytokines, TNF-? and IL-1?, in SAP rats. The inhibition of the p38 MAPK may be a potential target in the prevention and treatment of SAP.