**Basic Science**

VIII Preface

**Chapter 1**

**Sphingosine-1-Phosphate and Rheumatoid Arthritis:**

**Pathological Implications and Potential Therapeutic**

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 1% of the population worldwide. RA mainly targets the synovial tissues of the small joints of the hands and feet, although larger joints are also affected. The disease is characterized by 1) proliferation of synovial fibroblasts, leading to synovial hyperplasia; 2) recruitment of in‐ flammatory cells into joint tissue, resulting in tissue destruction; and 3) excessive secretion of pro-inflammatory cytokines/chemokines, contributing directly to synovium inflamma‐ tion. While the etiology of RA remains unknown, inflammatory mediators appear to drive the evolution of the disease. In particular, TNF-α together with proinflammatory cytokines, including IL-1β and IL-6, have been shown to be pivotal in promoting cytokine, chemokine and matrix metalloproteinase production within the RA synovium, along with cellular acti‐ vation and joint erosion [1,2]. Given the complexity of the inflammatory cascade in the RA synovium, it is of great importance to identify novel biochemical signalling moieties that

have the potential to constitute intracellular molecular checkpoints within the cell.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite which is formed from sphingosine by sphingosine kinases (SphKs) and degraded by S1P phosphatases (SPPs) and S1P lyase (SPL). S1P is critically involved in both physiological and pathological processes. The lipid is implicated in many cellular processes including proliferation, apoptosis and mi‐ gration via binding to and activation of its G protein-coupled cell surface receptors. Altera‐ tions in S1P signalling as well as in the enzymes involved in its synthesis and metabolism have been observed in many types of pathological situations such as angiogenesis, metasta‐ sis, and autoimmunity. Accumulating evidence now suggests a role for S1P in various as‐

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© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Targets**

Zhiyi Zhang and Chenqi Zhao

http://dx.doi.org/10.5772/53308

**1. Introduction**

Additional information is available at the end of the chapter
