Allergy therapy: the therapeutic potential of targeting sphingosine kinase signalling in mast cells

Melendez, A. J. (2008) Allergy therapy: the therapeutic potential of targeting sphingosine kinase signalling in mast cells. European Journal of Immunology, 38(11), pp. 2969-2974. (doi: 10.1002/eji.200838642)

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Mast cell activation is a central event in allergic diseases, and investigating the signalling pathways triggered during mast cell activation may lead to the discovery of novel therapeutic targets. Mast cells can be activated by a multitude of stimuli including antibodies/ antigen, cytokines/chemokines and neuropeptides, resulting in a variety of responses including the immediate release of potent inflammatory mediators. Moreover, recent data suggest that mast cell-mediated responses are also influenced by the differential sphingolipids/sphingosine to sphingosine-1-phosphate ratio. The importance of sphingolipids as potent biological mediators of both intracellular and extracellular responses is being increasingly recognized and accepted; it is now appreciated that activation of mast cells, via the high-affinity IgE-receptor (FcεRI) leads to the activation of sphingosine kinases (SphK), resulting in increased formation of sphingosine-1-phosphate. Furthermore, FcεRI activates SphK-dependent calcium mobilization in mast cells, leading to degranulation, cytokine, and eicosanoid production, and chemotaxis. In the past two years a critical role for SphK in allergic responses in vivo has emerged. In this review, I focus on the current understanding of the role of sphingosine kinases during mast cell signalling in vitro and their role during hypersensitivity responses in vivo, and discuss the potential of these enzymes as novel therapeutic targets to treat allergic diseases.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Melendez Romero, Dr Alirio
Authors: Melendez, A. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Immunology
Journal Abbr.:Eur. J. Immunol.
Publisher:Wiley-VCH Verlag
ISSN (Online):1521-4141
Published Online:16 October 2008
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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