Molecular mechanisms of chronic inflammaroty proliferative disease

慢性炎症增殖性疾病的分子机制

• 批准号: 06404023
• 负责人: HIRANO Toshio
• 金额: $ 21.06万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06404023/
• 关键词: rheumatoid arthritis; bone marrow stromal cell; BST-1; cytokine; IL-6; signal transduction; gene expression; inflammation

We have proposed a disease category which should be called as chronic inflammatory proliferative disease (CIPD). CIPD shows 1) chronic inflammation, 2) chronic proliferation of pathogenic cells, 3) involvement of immune response and 4) deregulated expression of multiple genes. We have analyzed gene products expressed in rheumatoid arthritis (RA), one of typical CIPD.We isolated novel cell surface molecules, BST-1 and BST-2 from RA-derived bone marrow stromal cells. We showed that certain severe RA patients have a large amount of soluble BST-1 in sera. Our trial to identify the molecular mechanisms which are involved in the deregulated expression of IL-6 in RA has not been successful, but we showed that human parvovirus product can induce IL-6 gene expression through NF-kappaB.We also elucidated the molecular mechanisms of interleukin 6, another molecule involved in CIPD.Our study showed that JAK-STAT signal transduction pathway plays critical roles in cell growth and survival.

我们提出了一个疾病类别，应被称为慢性炎症性增殖性疾病（CIPD）。CIPD显示1）慢性炎症，2）致病细胞的慢性增殖，3）免疫应答的参与和4）多个基因的表达失调。本研究分析了类风湿关节炎（RA）的基因表达产物，并从RA骨髓基质细胞中分离出新型细胞表面分子BST-1和BST-2。我们发现，某些严重的RA患者血清中有大量的可溶性BST-1。本研究试图阐明RA中IL-6表达失调的分子机制，但尚未成功，但我们发现人细小病毒产物可通过NF-κ B诱导IL-6基因表达，并阐明了另一种参与CIPD的分子IL-6的分子机制，我们的研究表明JAK-STAT信号转导通路在细胞生长和存活中起重要作用。

项目成果

Lee, B. O., et al.: "Elevated levels of the soluble form of bone marrow stromal cell antigen 1in the sera of patients with severe rheumatoid arthritis." Arthritis Rheum. 39. 629-637 (1996)

Lee, B. O. 等人：“严重类风湿性关节炎患者血清中可溶性骨髓基质细胞抗原 1 的水平升高。”

Fukuda, T., et al.: "Two signals are necessary for cell proliferation induced by a cytokine receptor gp130 : involvement of STAT3 in anti-apoptosis." Immunity. 5. 449-460 (1996)

Fukuda, T. 等人：“细胞因子受体 gp130 诱导的细胞增殖需要两个信号：STAT3 参与抗凋亡。”

Nakajima,K.,et al.: "Ann.New York Acad.Sci." Signal transduction through IL-6 receptor: involvement of multiple portein kinases, Stat factors and a novel H-7-sensitive pathway., 16 (1995)

Nakajima,K. 等人：“Ann.New York Acad.Sci”。

Matsuda,T.,et al.: "Association and activation of Fes tyrosine kinase by gp130,an IL-6 family cytokine signal transducer." J.Biol.Chem.(印刷中). (1995)

Matsuda, T. 等人：“gp130（IL-6 家族细胞因子信号转导器）对 Fes 酪氨酸激酶的关联和激活。”（J.Biol.Chem）（出版中）。

Okuyama, Y., et al.: "Human BST-1 expressed on myeloid cells functions as a receptor molecule." Biochem. Biophys. Res. Comm.228. 838-845 (1996)

Okuyama, Y. 等人：“在骨髓细胞上表达的人类 BST-1 充当受体分子。”