A study on altered immune function in rheumatoid arthritis through disfunction of transcription factor

转录因子功能障碍导致类风湿性关节炎免疫功能改变的研究

• 批准号: 07807051
• 负责人: INOUE Tetsufumi
• 金额: $ 1.34万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07807051/
• 关键词: apoptosis; transcripton factor; reactive oxygen species; anti-rheumatic drugs

NF-KB is known to play a important role in the regulation of macrophages. It is partially regulated by redox mechanism. In this study, anti-rheumatic drugs, D-penicillamine, bucillamine, auranofine increased the amount of intracellular reactive oxygen species of THP-1, moreover, downregulated their proliferation. It was suggested that these drugs suppressed the activity of NF-KB through the increase of reactive oxygen species.Possibility of the apoptosis induction through the increase of intracelllar reactive oxygen species was also studied. Bucillamine first induced the production of reactive oxygen species and the change of membrane permeability of THP-1. Consequently, apoptosis of THP-1 turned out. It was suggested that bucillamine suppressed the proliferation of synovial cells in rheumatoid arthritis through the induction of apoptosis.

已知 NF-KB 在巨噬细胞的调节中发挥重要作用。它部分受氧化还原机制调节。在本研究中，抗风湿药物D-青霉胺、布西拉明、金诺芬增加了THP-1细胞内活性氧的数量，并且下调了其增殖。提示这些药物通过增加活性氧来抑制NF-KB的活性。还研究了通过增加细胞内活性氧来诱导细胞凋亡的可能性。布西拉明首先诱导活性氧的产生和THP-1膜通透性的改变。结果，THP-1发生凋亡。有人认为布西拉明通过诱导细胞凋亡来抑制类风湿性关节炎滑膜细胞的增殖。

项目成果

広畑俊成: "インドメタシンファルネシルと慢性関節リウマチ患者末梢血単核球の相互作用" 日本臨床免疫学会会誌. 19. 136-144 (1996)

Toshinari Hirohata：“吲哚美辛法呢酯与类风湿性关节炎患者外周血单核细胞之间的相互作用”日本临床免疫学会杂志 19. 136-144 (1996)。

Sawada, T., Hashimoto, S., Hurukawa, H., Tohma, S., Inoue, T., Ito, K.: "Generation of reactive oxygen species is required for bucillamine, a novel anti-rheumatic drug, to induce apoptosis in concert with copper." Immunopharmacology. 35 (3). 195-202 (1996

Sawada, T.、Hashimoto, S.、Hurukawa, H.、Tohma, S.、Inoue, T.、Ito, K.：“布西拉明（一种新型抗风湿药）需要产生活性氧来诱导

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Shinohar,Satoshi: "Differential expression of Fas antigen and Bcl-2 protein on CD4_<1+>T cells,CD8_<1+>T cells and monooytes." Cellular Immunol.163. 303-308 (1995)

Shinohar，Satoshi：“Fas 抗原和 Bcl-2 蛋白在 CD4_<1>T 细胞、CD8_<1>T 细胞和单核细胞上的差异表达。”

Shinohara, S., Sawada, T., Nishioka, Y., Tohma, S., Kisaki, T., Inoue, T., et. al.: "Differential expression of Fas antigen and Bcl-2 protein on CD4^+ T cells, CD8^+ T cells and monocytes." Cellular Immmunol.163. 303-308 (1995)

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