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Published on: February 9, 2014
Expression of c-FLIP in a rat model of sepsis and its effects on endothelial apoptosis
Lei Shen1, Zhengda Sun2, Feng Zhao1
1Department of Intensive Care Unit, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Abstract:
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.
Insights
Cellular FLICE-inhibitory protein (c-FLIP) levels are lower in sepsis models, and higher c-FLIP expression reduces endothelial cell apoptosis. This suggests c-FLIP is important in sepsis pathogenesis and may offer therapeutic targets.
Area of Science:
- Immunology
- Cell Biology
- Pathophysiology
Background:
- Sepsis involves dysregulated inflammation and apoptosis.
- Cellular FLICE-inhibitory protein (c-FLIP) inhibits apoptosis.
- The role of c-FLIP in sepsis-induced endothelial cell apoptosis is unclear.
Purpose of the Study:
- To investigate the relationship between c-FLIP expression and sepsis.
- To determine the effect of c-FLIP on endothelial cell apoptosis in sepsis.
Main Methods:
- A rat model of sepsis was created using cecal ligation and puncture.
- Western blot analysis measured c-FLIPL protein expression in various tissues.
- In vitro experiments used c-FLIPL overexpression and flow cytometry to assess endothelial cell apoptosis.
Main Results:
- Sepsis rat models showed reduced c-FLIPL protein expression in the brain, intestine, and lung compared to controls.
- In vitro studies demonstrated an inverse correlation between c-FLIPL expression and endothelial cell apoptosis.
- Overexpression of c-FLIPL decreased endothelial cell apoptosis.
Conclusions:
- c-FLIP plays a significant role in sepsis.
- Reduced c-FLIP expression contributes to endothelial cell apoptosis in sepsis.
- c-FLIP modulation may represent a novel therapeutic strategy for sepsis.
