Induction of cytokines and ICAM-1 by proinflammatory cytokines in primary rheumatoid synovial fibroblasts and inhibition by N-acetyl-L-cysteine and aspirin
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概要
- 論文の詳細を見る
The role of transcription factor NF-кB in the induction of cytokines and ICAM-1 upon stimulation with proinflammatory cytokines, IL-1 and tumor necrosis factor (TNF)-α was investigated in primary synovial fibroblasts obtained from patients with rheumatoid arthritis (RA). Nuclear translocation of NF-кB was demonstrated after 30 min of treatment with IL-1 or TNF-α. Thereafter, the production of several cytokines including granulocyte macrophage colony stimulating factor, IL-6 and IL-8,that are known to be abundantly produced in the synovial cavity of RA patients, was greatly augmented. Similarly, cell surface expression of ICAM-1 was induced by the IL-1 or TNF-α treatment. Since expression of these genes is induced in rheumatoid synovial tissue, this experimental system is considered to represent the in vivo situation of RA pathophysiology. Using this cell culture system we attempted to modulate the intracellular signaling cascade for NF-кB activation and examined the effects of N-acetyl-L-cysteine (NAC) and acetylsalicylic acid (aspirin), which were previously reported to inhibit NF-кB activation. Pretreatment of the primary synovial fibroblasts with NAC inhibited nuclear translocation of NF-кB. Subsequently, the induction of these cytokines and ICAM-1 was considerably suppressed. On the other hand, pretreatment with aspirin blocked these phenomena only partially. These observations indicate the pivotal role of NF-кB in RA pathogenesis thus highlighting the possibility of a novel therapeutic strategy.
- 日本医科大学の論文
- 1997-03-25
著者
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OKAMOTO TAKASHI
Department of Pediatrics, Takamatsu Red Cross Hospital
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Sakurada Shinsaku
Department of Immunology and Infectious Diseases, Institute of Gerontology, Nippon Medical School
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KATO Tetsuji
Department of Molecular Genetics, Nagoya City University Medical School
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Okamoto T
Department Of Molecular And Cellular Biology Nagoya City University Graduate School Of Medical Scien
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Okamoto Takashi
Department Of Mechanical Engineering Fukuyama University
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Kato T
Department Of Molecular Genetics Nagoya City University Medical School
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Okamoto Takashi
Department Of Biological Sciences Tokyo Metropolitan University
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Sakurada Shinsaku
Department Of Molecular Genetics Nagoya City University Medical School
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Sakurada Shinsaku
Department Of Immunology And Infectious Diseases Institute Of Gerontology Nippon Medical School
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Okamoto Takashi
Department Of Animal Products National Institute Of Livestock And Grassland Science
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Okamoto Takashi
Department Of Agricultural Chemistry Faculty Of Agriculture Kinki University
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