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• W1549532175 endingPage "6034" @default.
• W1549532175 startingPage "6027" @default.
• W1549532175 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. Furthermore, use of antisense oligonucleotides to reduce expression of PLD1 or PLD2 demonstrated that PLD1 is required for TNF-alpha-induced production of several important cytokines, such as IL-1beta, IL-5, IL-6, and IL-13, in human monocytes. These studies demonstrate the critical role of PLD1 in the intracellular signaling cascades initiated by TNF-alpha and its functional role for coordinating the signals to inflammatory responses." @default.
• W1549532175 created "2016-06-24" @default.
• W1549532175 creator A5070054598 @default.
• W1549532175 creator A5079871204 @default.
• W1549532175 creator A5080935923 @default.
• W1549532175 date "2008-04-18" @default.
• W1549532175 modified "2023-10-13" @default.
• W1549532175 title "Phospholipase D1 Plays a Key Role in TNF-α Signaling" @default.
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• W1549532175 doi "https://doi.org/10.4049/jimmunol.180.9.6027" @default.
• W1549532175 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18424723" @default.
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