Expression of c-FLIP in a rat model of sepsis and its effects on endothelial apoptosis

摘要

Sepsis is characterized by the impaired regulation of inflammatory responses. Apoptosis is important in the pathogenesis of sepsis. Cellular FLICE-inhibitory protein (c-FLIP) is a catalytically inactive caspase-8 homologue, which negatively interferes with apoptotic signaling. The role of c-FLIP in sepsis and in endothelial cell apoptosis, a critical step in the pathogenesis of sepsis, remains controversial. In the present study, to investigate the relationship between c-FLIP and sepsis, a rat model of sepsis was induced by cecal ligation and puncture, and western blot analysis was used to detect the expression of c-FLIPL, the long isoform of c-FLIP. Lower protein expression levels of c-FLIPL were found in the brain, intestine and lung of the rat sepsis model, compared with the rats in the sham surgery group. The association between the expression of c-FLIPL and endothelial cell apoptosis was further examined in vitro by c-FLIPL overexpression and flow cytometry, which demonstrated that the expression of c-FLIPL was inversely correlated with endothelial cell apoptosis. These data suggested that c-FLIP may be important in sepsis and shed light on therapeutic strategies.