Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway

Figure 5

Proposed schematic mechanism of modulation of cell death. TLR4 signaling may modulate cell apoptosis related to the Bcl2 to Bax ratio in patients with sepsis. TLR4 inhibition using anti-TLR4 antibody might lead to an increase in Bcl2 to Bax ratio, which decreases Cyto C release from mitochondria. Activities of caspase-3, caspase-8, and caspase-9 did not change. Enhanced stimulation of RAGE might elevate pyroptosis, which increased cell death totally (TLR = toll-like receptor; Bcl2 = B cell lymphoma 2; Bax = Bcl2-associated X; Cyto C = cytochrome C; RAGE = receptor for advanced glycation end products; LPS = lipopolysaccharide; HMGB1 = high-mobility group box 1; TNF = tumor necrosis factor; TNFR = TNF receptor; ROS = reactive oxygen species; NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells).