(Specific Regulation of Mechanism of Hypercalcemia Induction in Adult T Cell Leukemia.)

（成人T细胞白血病高钙血症诱导机制的具体调控。）

• 批准号: 09470226
• 负责人: ETO Sumiya
• 金额: $ 5.25万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470226/
• 关键词: ATL; Hypercalcemia; Cell Adhesion Molecules; IL-1 gene; TAX protein; TAX蛋白; 細胞接着; LFA-1; イソテグン; G蛋白; Tax蛋白; IL-1β遺伝子; 核内転写因子

I.Results related with IL-1 (Bone resorption activating factor) gene Insertion of Human IL-1beta gene promotor fragmen with TAX protein which is producted by HTLV- I infection to Jurkat cells ; not HTLV-I infected T cell leukemia (ATL model) increased IL-1beta gene activity assayed by CAT compared with non- inserted cells. When the binding site in gene promortor of NF-IL6 or SP-1 which are the IL-1beta gene transactivators was muteted, this increse was completely blocked.Insertion of Human IL-1alpha cx gene promotor fragment with TAX protein also incresed IL-1alpha a gene activity. In this case, this increase was blocked by the mutation of binding site of NF- Kbeta which is the IL-1alpha gene transactivator.These results sugest that TAX protein is strongly involved with the production of IL-1, and the binding of NF-IL6, SP-1, NF-Kbeta to IL-1 gene promortor is essential for induction of IL-1 by TAX protein.II.Result related with adhesion moleculesIt is known that bone resorption is induced through osteoblast. Heterotypic adhesion of ATL cells and HOS cells ; osteoblast cell line, increased the expression of IL-1 mRNA in HOS cells and production of IL-1beta from HOS cells. In addition, this mRNA expression and protein production was significantly decreased by adding anti-VLA-4, LFA-1 antibody.Theses results sugest that adhesion of ATL cells and osteoblast through various adhesion molecules is also essential for producton of IL-1.

I. IL-1（骨吸收激活因子）基因的相关结果将人IL-1 β基因启动子片段插入HTLV-1感染的Jurkat细胞产生的TAX蛋白中，与未插入的细胞相比，未感染HTLV-1的T细胞白血病（ATL模型）通过CAT测定的IL-1 β基因活性增加。当突变IL-1 β基因反式激活因子NF-IL 6或SP-1基因启动子的结合位点时，这种增加被完全阻断，将人IL-1 α cx基因启动子片段插入TAX蛋白也能增加IL-1 α a基因的活性。在这种情况下，这种增加被IL-1 α基因反式激活因子NF-κ β结合位点的突变所阻断。这些结果表明，TAX蛋白强烈参与IL-1的产生，并且NF-IL 6，SP-1，NF-K β to IL-1基因启动子是诱导IL-1表达所必需的。II.与粘附分子相关的结果骨吸收是通过成骨细胞诱导的。ATL细胞与HOS细胞异型粘附后，HOS细胞IL-1 mRNA表达增加，HOS细胞IL-1 β产生增加。另外，加入抗VLA-4、LFA-1抗体后，这种mRNA的表达和蛋白质的产生明显减少，提示ATL细胞与成骨细胞通过各种粘附分子的粘附也是IL-1产生的必要条件。

项目成果

Mori, Naoki: "Characterization and regulation of interleukin-4 receptor in adult T cell leukemia cells." Eur.J.Haematol.56. 241-247 (1997)

Mori、Naoki：“成人 T 细胞白血病细胞中白细胞介素 4 受体的表征和调节。”

Okada,Yousuke: "Short term treatment of recombinant murine interleukin-4 rapidly inhibits bone formation in normal and overiectomized mine." Bone. 22. 361-368 (1998)

Okada, Yousuke：“重组鼠白细胞介素 4 的短期治疗可快速抑制正常和过度切除的小鼠的骨形成。”

Tsukada,J., Eto,S. 他: "HTLV-I Tax transactivates the promotor of human pro-IL-Iβ gene through association with two transcription factors,NF-IL6 and Spi-1" Blood. 90・8. 3142-3153 (1997)

Tsukada, J., Eto, S. 等人：“HTLV-I Tax 通过与两种转录因子 NF-IL6 和 Spi-1 关联来反式激活人 IL-Iβ 前体基因的启动子” Blood 90・8。 3142-3153 (1997)

Tanaka,Y., Eto,S. 他: "Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endotherial cells." J.Exp.Med.184・11. 1987-1997 (1997)

Tanaka, Y., Eto, S. 等人：“白血病细胞上的硫酸乙酰肝素蛋白聚糖主要参与整合素触发及其介导的内皮细胞粘附。”J.Exp.Med.184·11。 1997）

Tanaka,Yoshiya: "Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T cell lekemia cells." Blood. 91. 3309-3919 (1998)

Tanaka, Yoshiya：“组成型趋化因子的产生导致成人 T 细胞白血病细胞上白细胞功能相关抗原 1 的激活。”