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

1 .与IL-1（骨吸收激活因子）基因相关的结果HTLV- I感染Jurkat细胞后产生的TAX蛋白插入人IL-1 β基因启动子片段；非HTLV-I感染T细胞白血病（ATL模型）与未插入细胞相比，CAT检测il -1 β基因活性升高。当il -1基因反激活因子NF-IL6或SP-1基因启动子的结合位点被抑制时，这种增加被完全阻断。将人il - 1α - cx基因启动子片段与TAX蛋白一起插入也增加了il - 1α - a基因的活性。在这种情况下，这种增加被NF- Kbeta结合位点的突变所阻断，NF- Kbeta是il -1 α基因的反激活因子。这些结果表明，TAX蛋白强烈参与IL-1的产生，而NF-IL6、SP-1、nf - kβ与IL-1基因启动子的结合是TAX蛋白诱导IL-1的必要条件。2 .与粘附分子相关的结果。ATL细胞与HOS细胞的异型粘附；增加了HOS细胞中IL-1 mRNA的表达和HOS细胞中IL-1 β的产生。此外，添加抗vla -4、LFA-1抗体可显著降低该mRNA的表达和蛋白的产生。这些结果表明ATL细胞和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。

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.