Fig. 3

The death receptor signaling in SIVA. Death receptors (DR) signal is present also in alert cells of the major organs and vasculature in SIRS-associated vasculitis (SIVA) including sepsis. TNF-R1, Fas (CD95), DR4 (TRAIL receptor 1), and DR5 (TRAIL receptor 2) have a death signal in alert cells via adaptor molecules of TRADD and FADD. On the other side, TNF-R1 produces the anti-apoptotic factors such as FLIP and BclX via activation of NF-κB through RIP1-TRAF pathway. When NF-κB activity decreases and AP-1 activity increases, DR family and FADD tend to proceed apoptosis in alert cells in vascular endothelium. TNF-R1 tumor necrosis factor receptor 1, TRADD TNF receptor-associated death domain protein, RIP1 receptor-interacting protein 1, IKK inhibitory-κB kinase, TRAF tumor necrosis factor receptor-associated factor, FADD Fas-associated death domain protein, NF-κB nuclear factor-κB, FLIP FLICE inhibitory protein