| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
|
|---|
| Research Abstract |
Fibroblast-like synoviocytes(FLS) are among the principal effector cells in the pathogenesis of rheumatoid arthritis(RA). We recently reported the variety of stimulating effects of a proliferation-inducing ligand(APRIL), and its specific effect on the FLS in the affected RA synovium(RA-FLS). A significantly higher level of soluble APRIL was detected in RA serum than in normal serum. Among the three receptors of APRIL tested, RA-FLS expressed only B cell maturation antigen(BCMA), whereas the FLS in the affected osteoarthritis synovium(OA-FLS) expressed none of the receptors. APRIL stimulated RA-FLS but not OA-FLS to produce interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β and APRIL itself. APRIL also enhanced the receptor activator of nuclear factor kappaB ligand(RANKL) expression in RA-FLS.
The regulatory mechanisms of BCMA expression have not been fully described. OBF. 1 is a transcriptional co-activator, and has been shown to regulate the expression of PU. 1.In this study, we demonstrated that RA-FLS expressed transcription factor PU. 1 and transcriptional co-activator OBF. 1, and the expression levels of PU. 1 and OBF-1 were correlated with those of BCMA in RA-FLS.
These results provide evidence that APRIL is one of the main regulators in the pathogenesis of RA. Epigenetic regulation of BCMA transcription might contribute to the underlying mechanisms of this condition. Thus, both BCMA and APRIL could be considered as potential therapeutic targets in ameliorating damage to the affected joints of patients with RA.
|
