TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase
J. Clin. Invest. Jie Fan, et al. 112:1234 doi:10.1172/JCI18696 [Go to this article.]

Figure 7
Model of PMN NADPH oxidase–derived oxidant signaling in mediating the TLR4-TLR2 cross talk in endothelial cells. LPS stimulation induces NADPH oxidase activation and production of reactive oxygen species (ROS) in PMNs as well as the initiation of MyD88-dependent NF-κB signaling in endothelial cells and the consequent expression of TLR2 and ICAM-1. Adhesion of PMNs to endothelial cells is mediated by binding of constitutive ICAM-1 to CD18 integrin and provides the appropriate coupling required for PMNs to transmit oxidant signals to endothelial cells. The oxidants augment NF-κB signaling and TLR2 expression (+), which results in the augmented response of the cell to PGN, thereby amplifying ICAM-1 expression (circled +) and promoting stable adhesion of PMNs to endothelial cells and increased PMN migration. Thus, the PMN NADPH oxidase–mediated TLR4-TLR2 cross talk activates a positive feedback signal leading to sustained and amplified endothelial activation in response to invading pathogens.