Antisense oligonucleotides targeting c-fos mRNA inhibit rheumatoid synovial fibroblast proliferation

Abstract

Objective - To determine whether andsense oligonucleotides targeting c- fos mRNA have the ability to inhibit the growth of interleukin 1 (IL1) stimulated fibroblast-like cells from the synovium in rheumatoid arthritis (RA). Methods - Fibroblast-like cells established from RA synovium were stimulated by IL1 with antisense or sense oligonucleotides complementary to c-fos mRNA, and the proliferation of these cells was determined by 3H- thymidine incorporation. Effect of antisense ollgonucleotides on expression of activator protein 1 (AP1) activity was evaluated using electrophoretic mobility shift assay. Results - C-fos antisense oligonucleotides inhibited IL1 stimulated synovial fibroblast proliferation. The expression of AP1 activity induced by IL1 was suppressed by treatment with antisense oligonucleotides. Conclusion - These results suggest the feasibility of antisense strategies designed to suppress c-fos expression as therapeutic agents for RA.