Direct evidence of high DNA binding activity of transcription factor AP- 1 in rheumatoid arthritis synovium

Hiroshi Asahara, Koushi Fujisawa, Tetsuji Kobata, Tomoko Hasunuma, Toshiro Maeda, Masato Asanuma, Norio Ogawa, Hajime Inoue, Takayuki Sumida, Kusuki Nishioka

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Abstract

Objective. To investigate the possible activation of transcription factor AP-1 in rheumatoid arthritis (RA) and its involvement in the pathogenesis of RA. Methods. Synovial tissues and peripheral blood samples were obtained from 25 patients with RA and 5 patients with osteoarthritis (OA) during arthroplasty and synovectomy. The synovial tissue was digested with collagenase and separated into adherent and nonadherent cells by plastic-adhesion methods. Nuclear extracts obtained from each sample were examined by electrophoretic mobility shift assay to determine the DNA binding activity of AP-1. The expression of c-fos and c-jun messenger RNA (mRNA) was examined by in situ reverse transcription assay. Results. A markedly high DNA binding activity of AP-1 was detected in the synovial tissues of RA patients, while virtually no activity or only a little activity was observed in OA patients. Following separation of adherent and nonadherent cells, the AP-1 activity was mainly detected in adherent cells, which consisted of synovial cells and macrophages. However, the activity was significantly higher in the mononuclear cells infiltrating into RA synovium than in RA peripheral blood mononuclear cells. The high DNA binding activity of AP-1 in RA correlated with the expression of c-fos and c-jun mRNA in situ. Furthermore, AP-1 binding activity also correlated with disease activity. Conclusion. In RA synovium, AP-1 DNA binding activity was constitutively up-regulated. These findings suggest that AP-1 may play an important role in the pathogenesis of RA, including synovial hyperplasia and abnormal immune responses.

Original languageEnglish
Pages (from-to)912-918
Number of pages7
JournalArthritis and Rheumatism
Volume40
Issue number5
Publication statusPublished - 1997

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Synovial Membrane
Transcription Factor AP-1
Rheumatoid Arthritis
DNA
Osteoarthritis
Messenger RNA
Electrophoretic Mobility Shift Assay
Collagenases
Cell Adhesion
Arthroplasty
Plastics
Reverse Transcription
Hyperplasia
Blood Cells
Macrophages

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Asahara, H., Fujisawa, K., Kobata, T., Hasunuma, T., Maeda, T., Asanuma, M., ... Nishioka, K. (1997). Direct evidence of high DNA binding activity of transcription factor AP- 1 in rheumatoid arthritis synovium. Arthritis and Rheumatism, 40(5), 912-918.

Direct evidence of high DNA binding activity of transcription factor AP- 1 in rheumatoid arthritis synovium. / Asahara, Hiroshi; Fujisawa, Koushi; Kobata, Tetsuji; Hasunuma, Tomoko; Maeda, Toshiro; Asanuma, Masato; Ogawa, Norio; Inoue, Hajime; Sumida, Takayuki; Nishioka, Kusuki.

In: Arthritis and Rheumatism, Vol. 40, No. 5, 1997, p. 912-918.

Research output: Contribution to journalArticle

Asahara, H, Fujisawa, K, Kobata, T, Hasunuma, T, Maeda, T, Asanuma, M, Ogawa, N, Inoue, H, Sumida, T & Nishioka, K 1997, 'Direct evidence of high DNA binding activity of transcription factor AP- 1 in rheumatoid arthritis synovium', Arthritis and Rheumatism, vol. 40, no. 5, pp. 912-918.
Asahara, Hiroshi ; Fujisawa, Koushi ; Kobata, Tetsuji ; Hasunuma, Tomoko ; Maeda, Toshiro ; Asanuma, Masato ; Ogawa, Norio ; Inoue, Hajime ; Sumida, Takayuki ; Nishioka, Kusuki. / Direct evidence of high DNA binding activity of transcription factor AP- 1 in rheumatoid arthritis synovium. In: Arthritis and Rheumatism. 1997 ; Vol. 40, No. 5. pp. 912-918.
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AU - Kobata, Tetsuji

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AU - Maeda, Toshiro

AU - Asanuma, Masato

AU - Ogawa, Norio

AU - Inoue, Hajime

AU - Sumida, Takayuki

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