Sphingosine kinase 1 regulates pro-inflammatory responses triggered by TNFα in primary human monocytes

Zhi, L., Leung, B.P. and Melendez Romero, A.J. (2006) Sphingosine kinase 1 regulates pro-inflammatory responses triggered by TNFα in primary human monocytes. Journal of Cellular Physiology, 208(1), pp. 109-115. (doi: 10.1002/jcp.20646)

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Monocytes play an important role in inflammation, angiogenesis, and atherosclerosis. During these processes monocytes release pre-formed proinflammatory mediators from granules, and synthesize de novo cytokines and chemokines important in the amplification of the inflammatory response. One of the most prominent triggers of inflammatory responses is the cytokine TNFα. However, the intracellular signaling cascades triggered by TNFα are not fully understood. In this study we investigated the roles of SPHK on the TNFα-triggered responses on human primary monocytes. We show that TNFα rapidly triggers S1P generation and activation of SPHK. Moreover, our data shows that SPHK1 is the isoform activated by TNFα, and plays an essential role on the TNFα-triggered intracellular Ca2+ signals, degranulation, cytokine production, and activation of NFκB, thus suggesting a pivotal role for SPHK1 on the proinflammatory responses triggered by TNFα.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Melendez Romero, Dr Alirio and Leung, Dr Bernard
Authors: Zhi, L., Leung, B.P., and Melendez Romero, A.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Cellular Physiology
Journal Abbr.:J. Cell Physiol.
Publisher:John Wiley & Sons, Inc.
ISSN (Online):1097-4652
Published Online:30 March 2006

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
462311Therapeutic potential of Sphingosine Kinase blockage in allergic anaphylaxis.Alirio Melendez RomeroMedical Research Council (MRC)G0700794Institute of Infection Immunity and Inflammation