Exposure of resting endothelial cells to TNF-α or LPS leads to increased expression of the P2Y₆ purinergic receptor. Simultaneous or subsequent injury to the endothelium promotes the release of UTP/UDP the endogenous ligands of the P2Y₆ receptor. These 2 events serve to up-regulate NF-KB signaling leading to increased IL-8 and VCAM-1 expression to collectively enhance tissue inflammation. This model was derived from experiments by Riegel and colleagues¹  demonstrating that genetic removal or pharmacologic inhibition of P2Y₆ lead to attenuation of these pathways.