Shinohara M, Morisawa K, Ota K, Qu Z, Takeda K, Hashimoto K, Tomoda T, Kurashige T, Taniguchi T
Department of Pediatrics, Kochi Medical School, Japan.
Cell Mol Biol (Noisy-le-grand). 1997 Mar;43(2):227-35.
The expression of MHC class II molecules is normally restricted to antigen presenting cells. Aberrant expression of class II molecules, however, was detected in the thyrocytes of autoimmune thyroid diseases. We attempted to regulate the expression of HLA-DR molecules in thyroid carcinoma cells by expressing the exogenous poly(ADP-ribose) synthetase gene. We transfected a metal inducible expression plasmid capable of expressing poly(ADP-ribose) synthetase gene into thyroid carcinoma 8505C cells and the transformants, treated with metal and IFN-gamma, were separated by Magnetic Cell Separation. The activity of the synthetase was increased in the HLA-DR-enriched transformants as compared with that in control or the HLA-DR+ transformants. RNA blot analysis and flow cytometric analysis revealed that the IFN-gamma-inducible expression of HLA-DR molecules was depressed by the induction of exogenous poly(ADP-ribose) synthetase gene. This result indicates that HLA-DR expression was correlated with the level of poly(ADP-ribose) synthetase in human thyroid carcinoma cells. Furthermore we examined the level of poly(ADP-ribose) synthetase in patients with autoimmune thyroid diseases. We observed a significant decrease in poly(ADP-ribose) synthetase in the patients. Taken together with the previous observation, the decrease in poly(ADP-ribose) synthetase is closely linked to the aberrant expression of HLA-DR molecules in some autoimmune thyroid diseases.
MHC II类分子的表达通常局限于抗原呈递细胞。然而，在自身免疫性甲状腺疾病的甲状腺细胞中检测到了II类分子的异常表达。我们试图通过表达外源性聚（ADP-核糖）合成酶基因来调节甲状腺癌细胞中HLA-DR分子的表达。我们将能够表达聚（ADP-核糖）合成酶基因的金属诱导表达质粒转染到甲状腺癌8505C细胞中，并用金属和干扰素-γ处理转化体，通过磁性细胞分离法进行分离。与对照或HLA-DR+转化体相比，富含HLA-DR的转化体中合成酶的活性增加。RNA印迹分析和流式细胞术分析表明，外源性聚（ADP-核糖）合成酶基因的诱导抑制了干扰素-γ诱导的HLA-DR分子表达。该结果表明，在人甲状腺癌细胞中HLA-DR的表达与聚（ADP-核糖）合成酶的水平相关。此外，我们检测了自身免疫性甲状腺疾病患者体内聚（ADP-核糖）合成酶的水平。我们观察到患者体内聚（ADP-核糖）合成酶显著降低。结合之前的观察结果，聚（ADP-核糖）合成酶的降低与某些自身免疫性甲状腺疾病中HLA-DR分子的异常表达密切相关。
