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World J Biol Chem. Nov 26, 2010; 1(11): 321-326
Published online Nov 26, 2010. doi: 10.4331/wjbc.v1.i11.321
Role of sphingosine kinase and sphingosine-1-phosphate in inflammatory arthritis
Wen-Qi Lai, Alirio J Melendez, Bernard P Leung
Wen-Qi Lai, Alirio J Melendez, Bernard P Leung, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Alirio J Melendez, Bernard P Leung, Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G11 8TA, United Kingdom
Author contributions: Lai WQ, Melendez AJ, Leung BP wrote and revised the manuscript.
Correspondence to: Bernard P Leung, PhD, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, MD9, Singapore 117597, Singapore. phslplb@nus.edu.sg
Telephone: +65-65164227 Fax: +65-67788161
Received: July 20, 2010
Revised: August 20, 2010
Accepted: August 27, 2010
Published online: November 26, 2010
Abstract

The importance of sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) in inflammation has been extensively demonstrated. As an intracellular second messenger, S1P plays an important role in calcium signaling and mobilization, and cell proliferation and survival. Activation of various plasma membrane receptors, such as the formyl methionyl leucyl phenylalanine receptor, C5a receptor, and tumor necrosis factor α receptor, leads to a rapid increase in intracellular S1P level via SphK stimulation. SphK and S1P are implicated in various chronic autoimmune conditions such as rheumatoid arthritis, primary Sjögren’s syndrome, and inflammatory bowel disease. Recent studies have demonstrated the important role of SphK and S1P in the development of arthritis by regulating the pro-inflammatory responses. These novel pathways represent exciting potential therapeutic targets.

Keywords: Cytokines, Inflammation, Rheumatoid arthritis, Sphingosine kinase, Sphingosine-1-phosphate