Potential role of sphingosine 1-phosphate in the pathogenesis of rheumatoid arthritis

In summary, S1P functions through multiple receptors, of which three are expressed in fibroblast-like synoviocytes, a cell type that appears to malfunction in rheumatoid arthritis. Bourgoin and colleagues demonstrated the role of these receptors in synoviocyte migration, survival, and inflammatory cytokine production, processes that are involved in the pathophysiology of rheumatoid arthritis. Furthermore, these authors showed that pretreatment of fibroblast-like synoviocytes with TNFa increases expression of the S1P3 receptor and enhances inflammatory cytokine/chemokine production in response to this agent, an effect that probably serves to exacerbate the disease process. Thus, the results reported here suggest the possibility of using S1P receptor antagonists and/or inhibitors of sphingosine kinase, either alone or in combination with drugs that target the TNFa pathway, for the treatment of rheumatoid arthritis.