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


CONCLUSIONS
These results suggest the feasibility of antisense strategies designed to suppress c-fos expression as therapeutic agents for RA.
Morita
Y
Y
Department of Medicine III, Okayama University Medical School, Japan.
Kashihara
N
N
Yamamura
M
M
Okamoto
H
H
Harada
S
S
Kawashima
M
M
Makino
H
H
D001172:Arthritis, Rheumatoid / Q000473:pathology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000235:genetics; D018390:Gene Targeting / Q000379:methods*; D018398:Homeodomain Proteins; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D015778:Minor Histocompatibility Antigens; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013583:Synovial Membrane / Q000473:pathology*
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007375:Interleukin-1; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051818:Replication Protein C