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Antisense oligonucleotides targeting c-fos mRNA inhibit
rheumatoid synovial fibroblast proliferation
Department of Medicine III, Okayama University Medical
School, Okayama, Japan
Correspondence to: Dr N Kashihara, Department of Medicine III, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700, Japan.
Accepted for publication 19 November 1997
OBJECTIVE
To determine whether antisense
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).
METHODSFibroblast-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 oligonucleotides on expression of activator protein
1 (AP1) activity was evaluated using electrophoretic mobility shift assay.
RESULTSC-fos antisense oligonucleotides inhibited
IL1 stimulated synovial fibroblast proliferation. The expression of
AP1 activity induced by IL1 was suppressed by treatment with antisense oligonucleotides.
CONCLUSIONThese results suggest the feasibility
of antisense strategies designed to suppress c-fos expression as
therapeutic agents for RA.
© 1998 by Annals of the Rheumatic Diseases
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