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靶向c-fos信使核糖核酸的反义寡核苷酸抑制类风湿性滑膜成纤维细胞增殖。

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

作者信息

Morita Y, Kashihara N, Yamamura M, Okamoto H, Harada S, Kawashima M, Makino H

机构信息

Department of Medicine III, Okayama University Medical School, Japan.

出版信息

Ann Rheum Dis. 1998 Feb;57(2):122-4. doi: 10.1136/ard.57.2.122.

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.

摘要

目的

确定靶向c-fos mRNA的反义寡核苷酸是否有能力抑制类风湿关节炎(RA)中白细胞介素1(IL1)刺激的滑膜成纤维样细胞的生长。

方法

用与c-fos mRNA互补的反义或正义寡核苷酸刺激从RA滑膜建立的成纤维样细胞,通过3H-胸苷掺入法测定这些细胞的增殖。使用电泳迁移率变动分析评估反义寡核苷酸对活化蛋白1(AP1)活性表达的影响。

结果

c-fos反义寡核苷酸抑制IL1刺激的滑膜成纤维细胞增殖。用反义寡核苷酸处理可抑制IL1诱导的AP1活性表达。

结论

这些结果表明,设计用于抑制c-fos表达的反义策略作为RA治疗药物具有可行性。

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