TNF-α Induces Neutrophil Apoptosis Delay and Promotes Intestinal Ischemia-Reperfusion-Induced Lung Injury through Activating JNK/FoxO3a Pathway

Figure 8

Schematic illustration of the mechanism of TNF-α-induced delay in polymorphonuclear neutrophil (PMN) apoptosis that promotes intestinal ischemia-reperfusion- (IIR-) induced lung injury via activating FoxO3a. TNF-α releases into the circulation and activates macrophages to produce a large amount of TNF-α during intestinal ischemia-reperfusion. TNF-α subsequently promotes the dissociation of FoxO3a from Sirt1 into the nucleus by activating the JNK pathway in neutrophil, which promotes the transcription of Bim and inhibits the transcription of Bcl-2, resulting in delayed neutrophil apoptosis and thus induces acute lung injury. Moreover, IL-1β released by macrophages may also activate nuclear translocation of FoxO3a through the PI3K/AKT pathway in neutrophil.