Saturday, October 29, 2011
Hall 1-2 (San Jose Convention Center)
Rheumatoid arthritis (RA) affects approximately 1% of the adult worldwide population. RA is characterized by chronic inflammation, cartilage destruction, and joint deformity. These hallmarks of RA cause significant disability and decreased quality of life for patients with RA, therefore development of new drug therapeutics to reduce symptoms is of fundamental importance. The underlying causes of development of RA are unclear. However, the activation of macrophages, B cells, mast cells, fibroblast-like synoviocytes (FLSs) and CD4+T lymphocytes are known to contribute to synovial inflammation and joint destruction. Sphingosine 1- phosphate (S1P) is involved in trafficking and migration of various types of immune cells. S1P is generated by phosphorylation of sphingosine mediated by sphingosine kinase 1 (SphK1) and sphingosine kinase 2(SphK2). Prior studies have suggested opposing roles for the sphingosine kinases in inflammatory processes of RA. While targeting of SphK1 with siRNA seemed to reduce inflammation, animals in which SphK2 was targeted with siRNAs developed a more aggressive disease. Deficiency of SphK1 has also been shown to diminish RA symptoms in model of TNFa induced RA. In our work we use genetically altered mice, deficient in SphK1 and SphK2, to study their role in the development of inflammation and arthritis in an antibody-driven collagen-induced arthritis (CIA) model. The advantage of using this CIA model is that it allows studying the inflammatory phase of the disease without involving the priming phase of the immune response. This should allow distinguishing of the roles of SphK1 and 2 in cells that promote arthritis.