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https://doi.org/10.24546/00098332
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2024-03-30
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00098332 (fulltext)
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メタデータID
00098332
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open access
出版タイプ
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タイトル
Inhibition of DNA Duplication of Rheumatoid Synovial Fibroblast by N'-[β-D-Ribofuranosyl-5-hydroxyimidazol-4-carboxamide, Mizoribine
著者
Saura, Ryuichi ; Tomioka, Masao ; Hirata, Soichiro ; Ishikawa, Hitoshi
著者名
Saura, Ryuichi
著者名
Tomioka, Masao
著者名
Hirata, Soichiro
著者名
Ishikawa, Hitoshi
収録物名
Bulletin of health sciences Kobe
巻(号)
17
ページ
35-41
出版者
Graduate School of Health Sciences, Kobe University
刊行日
2001-11-30
公開日
2006-09-11
注記
本文ファイルは、国立情報学研究所CiNiiより提供されたものです。
抄録
The hyperplasia of synovial fibroblast plays critical roles in the propagation of rheumatoid synovitis. N'-[β-D-Ribofuranosyl]-5-hydroxyimidazol-4-carboxamide (mizoribine; MZR), an immunosuppressive agent, is reported to have beneficial effects in patients with rheumatoid arthritis (RA) for suppression of lymphocyte proliferation. In order to study the anti-rheumatic action of MZR, we have investigated its effect on DNA synthesis of RA synovial fibroblasts. DNA synthesis by synovial fibroblasts was evaluated by measuring the uptake of tritiated thymidine (^3H-TdR) after stimulation with interleukin-1β in the presence or absence of MZR. MZR suppressed ^3H-TdR incorporation by synovial fibroblasts in a concentration-dependent manner. This inhibition was significant with 1-2μg/ml MZR (p<0.01), the concentration attainable in sera of treated patients. MZR has been reported to inhibit inosine monophosphate (IMP) dehydrogenase, a key enzyme in the formation of guanine ribonucleotides from IMP. Therefore, to examine whether this suppression of cell proliferation by MZR is also due to the inhibition of IMP dehydrogenase, guanosine monophosphate (GMP), an end-product converted by IMP dehydrogenase, and MZR were added simultaneously to synovial fibroblast cultures. We found that 10μg/ml of GMP reversed the MZR-induced suppression of synovial fibroblast proliferation. These results suggest that MZR inhibits synovial fibroblast proliferation directly by depleting of intracellular guanine ribonucleotides, thereby possibly inhibiting rheumatoid synovitis by virtue of this action.
キーワード
Synovial fibroblast
Pannus formation
Interleukin-1β
Rheumatoid arthritis
N'-[β -D-Ribofuranosyl]-5-hydroxyimidazol-4-carboxamide
Mizorihine
カテゴリ
Bulletin of health sciences Kobe
>
17号(2001-11-30)
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資源タイプ
departmental bulletin paper
言語
English (英語)
ISSN
1346-8707
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NCID
AA11316362
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関連情報
NAID
110004599719
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