FIG. 6.

Signaling events mediating TNFαa-induced ICAM-1 expression in endothelial cells. Stimulation of TNF receptor triggers the activation of PI3Kγ, which in turn activates PKCζ. Activated PKCζ induces the activation of NADPH oxidase resulting in ROS generation, which in turn promotes RelA/p65 homodimer binding to the ICAM-1 promoter through phosphorylation and degradation of IκBα. PKCζ also phosphorylates, and thereby amplifies the transactivation potential of the bound RelA/p65. The resultant ICAM-1 expression promotes the stable adhesion of leukocytes to endothelial cells.