Phospholipase D1 plays a key role in TNF-alpha signaling.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Swaminathan SethuA J Melendez

Abstract

The primary characteristic features of any inflammatory or infectious lesions are immune cell infiltration, cellular proliferation, and the generation of proinflammatory mediators. TNF-alpha is a potent proinflammatory and immuno-regulatory cytokine. Decades of research have been focused on the physiological/pathophysiological events triggered by TNF-alpha. However, the signaling network initiated by TNF-alpha in human leukocytes is still poorly understood. In this study, we report that TNF-alpha activates phospholipase D1 (PLD1), in a dose-dependent manner, and PLD1 is required for the activation of sphingosine kinase and cytosolic calcium signals. PLD1 is also required for NFkappaB and ERK1/2 activation in human monocytic cells. Using antisense oligonucleotides to reduce specifically the expression of PLD isozymes showed PLD1, but not PLD2, to be coupled to TNF-alpha signaling and that PLD1 is required to mediate receptor activation of sphingosine kinase and calcium transients. In addition, the coupling of TNF-alpha to activation of the phosphorylation of ERK1/2 and the activation of NFkappaB were inhibited by pretreating cells with antisense to PLD1, but not to PLD2; thus, demonstrating a specific requirement for PLD1. Furth...Continue Reading

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Citations

Oct 23, 2010·Bioscience Reports·Swaminathan Sethu, Alirio J Melendez
Jan 15, 2014·International Journal of Clinical Rheumatology·Ashley J Snider
Jul 4, 2018·Scientific Reports·Marc-Andre UrbahnMargitta Elvers
Mar 9, 2011·Neurochemical Research·Susan A AustinColin K Combs
Apr 7, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Priya D A IssureeAlirio J Melendez
May 31, 2011·Immunology Letters·Mi Kyung ParkSung-Hwan Park

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