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Antisense oligonucleotides targeting c-fos mRNA inhibit rheumatoid synovial fibroblast proliferation
Y Morita1, N Kashihara, M Yamamura
1Department of Medicine III, Okayama University Medical School, Japan.
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).
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 oligonucleotides 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.
Insights
Antisense oligonucleotides targeting c-fos messenger RNA (mRNA) successfully inhibited the growth of interleukin 1 (IL1) stimulated fibroblast-like cells in rheumatoid arthritis (RA). This suggests a potential new therapeutic strategy for RA by suppressing c-fos expression.
Area of Science:
- Molecular biology
- Immunology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) involves inflammation of synovial fibroblast-like cells.
- Interleukin 1 (IL1) is a key cytokine in RA pathogenesis.
- The c-fos gene and its protein product are implicated in cellular proliferation.
Purpose of the Study:
- To investigate the efficacy of antisense oligonucleotides targeting c-fos mRNA.
- To determine if these oligonucleotides can inhibit IL1-stimulated synovial fibroblast proliferation in RA.
Main Methods:
- Fibroblast-like cells from RA synovium were cultured and stimulated with IL1.
- Cells were treated with antisense or sense oligonucleotides against c-fos mRNA.
- Proliferation was measured using 3H-thymidine incorporation; AP1 activity was assessed via electrophoretic mobility shift assay.
Main Results:
- C-fos antisense oligonucleotides significantly inhibited IL1-stimulated synovial fibroblast proliferation.
- The expression of activator protein 1 (AP1) activity, induced by IL1, was suppressed by antisense treatment.
Conclusions:
- Antisense strategies targeting c-fos mRNA show promise for RA therapy.
- Suppression of c-fos expression may be a viable approach to control RA progression.