Abstract
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.
MeSH terms
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Arthritis, Rheumatoid / pathology*
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Cell Culture Techniques
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Cell Division / drug effects
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DNA-Binding Proteins / metabolism
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Fibroblasts / drug effects*
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Fibroblasts / immunology
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Gene Expression / genetics
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Gene Targeting / methods*
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Homeodomain Proteins*
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Humans
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Interleukin-1 / immunology
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Minor Histocompatibility Antigens
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Oligonucleotides, Antisense / pharmacology*
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Proto-Oncogene Proteins c-bcl-2*
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Proto-Oncogene Proteins c-fos / genetics*
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RNA, Messenger / genetics
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Replication Protein C
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Repressor Proteins*
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Saccharomyces cerevisiae Proteins*
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Synovial Membrane / pathology*
Substances
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BCL2-related protein A1
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DNA-Binding Proteins
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Homeodomain Proteins
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Interleukin-1
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MATA1 protein, S cerevisiae
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Minor Histocompatibility Antigens
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Oligonucleotides, Antisense
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-fos
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RNA, Messenger
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Replication Protein C