Phospholipase D1 Plays a Key Role in TNF-α Signaling

摘要: The primary characteristic features of any inflammatory or infectious lesions are immune cell infiltration, cellular proliferation, and the generation proinflammatory mediators. TNF-alpha is a potent immuno-regulatory cytokine. Decades research have been focused on physiological/pathophysiological events triggered by TNF-alpha. However, signaling network initiated in human leukocytes still poorly understood. In this study, we report that activates phospholipase D1 (PLD1), dose-dependent manner, PLD1 required for activation sphingosine kinase cytosolic calcium signals. also NFkappaB ERK1/2 monocytic cells. Using antisense oligonucleotides to reduce specifically expression PLD isozymes showed PLD1, but not PLD2, be coupled mediate receptor transients. addition, coupling phosphorylation were inhibited pretreating cells with PLD2; thus, demonstrating specific requirement PLD1. Furthermore, use PLD2 demonstrated TNF-alpha-induced production several important cytokines, such as IL-1beta, IL-5, IL-6, IL-13, monocytes. These studies demonstrate critical role intracellular cascades its functional coordinating signals responses.