Therefore, it is not surprising that much effort has been directed at blocking TNFa in human diseases; however, with mixed success. Incidentally, in spite of a great body of literature on the inflammatory pathways triggered by TNFa in various cell types, no significant validation of potential signaling targets has been documented. We recently reported that in human monocytes, TNFa activates the Phosphatidylcholine-specific Phospholipase D1, and showed that inhibition of PLD-generated active products, or genetic-silencing of PLD1, largely inhibits TNFa-triggered key intracellular signaling pathways pivotal in the TNFa-mediated proinflammatory responses, suggesting a potential role for PLD1 in TNFa-mediated inflammation. Phosphatidylcholine, in addition to being a structural constituent of cell membranes, is a source of important signaling molecules. In particular, PC-derived phosphatidic acid and diacylglycerol have emerged as a new class of potent bioactive molecules, Clindamycin palmitate HCl implicated in a Fomepizole variety of cellular processes, such as cell differentiation, apoptosis, and proliferation. Phosphatidylcholine-specific Phospholipase D is the enzyme which hydrolyzes phosphatidylcholine, to generate phosphatidic acid and choline. PA, a potent second messenger by itself, can be dephosphorylated to Diacylglycerol, or hydrolyzed to Lyso-phosphatidic acid, by Phosphatidic acid phosphohydrolases and Phospholipase A2 respectively. Intracellularly, PLD, or its product PA, is known to regulate a variety of homeostatic cellular functions such as membrane trafficking, vesicular transport, cytoskeletal re-organization, cellular migration, proliferation and survival. A role of PLD in immune cell responses in vitro is supported by a variety of studies showing PLD to mediate receptor-activated effector responses, including in phagocytosis, NADPH-oxidative burst, immune cell migration, degranulation and cytokine production. PLD comprises two major isoforms, PLD1 and PLD2, expressed in a wide range of almost all the mammalian tissues.PLD1 has been associated with the activation of monocytes/macrophages, neutrophils and mast cells, whereas PLD2 has been associated with responses in T lymphocytes. However, due to lack of isoform-specific inhibitors for in vivo work and knockout mice, the role of PLDs, and indeed of individual PLD isoforms in in vivo physiology or pathophysiology remains largely unknown.