Induction of NLRP3 Inflammasome Activation by Heme in Human Endothelial Cells

Figure 9

Working model of heme-induced NLRP3 inflammasome activation in endothelial cells. Pathogen-associated molecular patterns (PAMPs), such as LPS or TNF (Signal 1), bind to toll-like receptors (TLRs) or TNF receptor and prime endothelial cells to activate NF-κB to induce the expression of NLRP3, caspase-1, and IL-1β. Heme (signal 2) that can derive from Hb released form damaged RBCs induces ROS generation, caspase-1 activation, and cleavage of pro-IL-1β. Mature form of IL-1β is secreted from the cell. The role of K⁺ efflux and lysosomal destabilization remained to be explored.