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Title: The role of Sphingosine kinase in inflammatory diseases
Authors: LAI WENQI
Keywords: Sphingosine Kinase, Sphingosine-1-phosphate, Asthma, Rheumatoid Arthritis, Inflammatory diseases
Issue Date: 11-Aug-2009
Citation: LAI WENQI (2009-08-11). The role of Sphingosine kinase in inflammatory diseases. ScholarBank@NUS Repository.
Abstract: Sphingosine kinase (SphK) is a key enzyme in the sphingolipid metabolic pathway responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P). Previous studies have shown a pivotal role for SphK/S1P in several inflammatory responses and pathophysiologic conditions. We found that administration of DMS, a potent SphK inhibitor, as well as siRNA targeting SphK1 isoform, attenuates the severity of OVA-induced asthma and collagen-induced arthritis (CIA) in the mice. This is mediated through a reduction inflammatory infiltrates into the inflammed tissues, reduction in pro-inflammatory cytokines levels in vivo, as well as, attenuation of antigen-specific immune responses in cultured lymph node cells. On the other hand, mice administered with SphK2 siRNA develop a more aggressive disease. Together, these results demonstrate the distinct immunomodulatory roles of SphK1 and SphK2 in the development of inflammatory diseases. These findings raise the possibility that drugs targeting SphK1 activity may play a beneficial role in the treatment of such diseases.
Appears in Collections:Ph.D Theses (Open)

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