THU0063 Cellular RA-Binding Protein (CRABP)-II Suppression Sensitizes Rheumatoid Fibroblast-Like Synoviocytes to FAS-Induced Apoptosis

Background Disregulated proliferation and apoptosis of fibroblast-like synoviocytes (FLS) contribute to synovial hyperplasia, chronic inflammation and tissue damage in rheumatoid arthritis (RA). Therefore, FLS are a potential target for therapy given that current treatments, focused against inflammatory factors, are not fully effective in a significant number of patients. An unexplored area includes vitamine A and its metabolites, known as retinoids. They regulate cellular proliferation, differentiation and apoptosis. As such, they have a potent pro-apoptotic and anti-proliferative activity in some types of cancer. The retinoids are transported to the nucleus by the intracellular proteins CRABP-II and FABP5, which expression ratio (CRABP-II/FABP5) determines opposite effects of retinoids. In cells with a high ratio, retinoids signal through RAR and activate pro-apoptotic genes, whereas in cells with a low ratio, they signal through PPARβ/δ and promote survival responses. Objectives To analyse the role of retinoids, and CRABP-II and FABP5 proteins in proliferation and apoptosis of RA FLS. Methods FLS were obtained from 7 RA patients. CRABP-II and FABP5 expression was analyzed by real-time PCR and by western blot. TNF-induced proliferation was determined using the CellTiter-Glo luminescent viability assay (Promega). Fas-induced apoptosis was analyzed with the cell death ELISA kit (Roche). Expression of CRABP-II and FABP5 was suppressed in RA FLS by siRNA transfection. Results CRABP-II and FABP5 expression was analysed in RA FLS. TNF stimulation increased the expression of FABP5 as compared with the baseline ( p p p p Next, we analysed the effect of ATRA on Fas-induced apoptosis. Treatment with ATRA decreased RA FLS apoptosis ( p To distinguish the role of CRABP-II and FABP5 in these effects, we suppressed each of them in RA FLS by siRNA transfection. The lack of CRABP-II sensitized RA FLS to Fas induced apoptosis ( p FABP5 knockdown did not modify the response of RA FLS to Fas-induced apoptosis. Conclusions Overall these results suggest that retinoid signalling pathway could be involved in the FLS pathogenic changes in RA. Disclosure of Interest None declared