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Title: Role of PLD and SPHK in TNFa induced signaling and inflammatory responses
Keywords: Inflammation, TNFa, Phospholipase D, Sphingosine kinase, intracellular signaling, Peritonitis.
Issue Date: 2-Jan-2009
Citation: SWAMINATHAN SETHU (2009-01-02). Role of PLD and SPHK in TNFa induced signaling and inflammatory responses. ScholarBank@NUS Repository.
Abstract: PLD (Phospholipase D) and SphK (Sphingosine kinase) play a vital role in immune cell responses. TNFa (Tumor Necrosis Factor alpha), a potent pro-inflammatory cytokine, is important in triggering and amplifying inflammatory responses. The study investigated the role of PLD and SphK in TNFa-induced signaling events and effector responses. This study revealed that TNFa induces PLD activity and translocation of PLD1. The study also showed, PLD is essential in TNFa-triggered ERK1/2 activation, but not p38-phosphorylation. TNFa triggered activation of SphK, NFkB, cytokine production and chemotaxis were also mediated by PLD. Antisense based investigation revealed the coupling of PLD1 to TNFa signaling events and responses. Furthermore, the role for PLD1 and SphK1 in TNFa-induced peritonitis in mice was validated using RNA interference. Collectively, the results indicate a pivotal role for PLD1 and SphK1 in TNFa-triggered inflammatory responses and suggest their potential in the therapeutic management of inflammatory disorders.
Appears in Collections:Ph.D Theses (Open)

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