RECOMBINANT HUMAN INTERFERON-GAMMA EXERTS AN ANTIPROLIFERATIVE EFFECT AND MODULATES THE EXPRESSION OF HUMAN-LEUKOCYTE ANTIGEN-A, ANTIGEN-B, ANTIGEN-C AND ANTIGEN-DR IN HUMAN UROTHELIAL CELL-LINES
RECOMBINANT HUMAN INTERFERON-GAMMA EXERTS AN ANTIPROLIFERATIVE EFFECT AND MODULATES THE EXPRESSION OF HUMAN-LEUKOCYTE ANTIGEN-A, ANTIGEN-B, ANTIGEN-C AND ANTIGEN-DR IN HUMAN UROTHELIAL CELL-LINES
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DOI：
10.1007/bf01742372
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发表时间：
1990-03-01
影响因子：
5.8
通讯作者：
KIELER, J
中科院分区：
文献类型：
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作者：
OTTESEN, SS;AHRENKIEL, V;KIELER, J
在这项研究中，我们用重组人干扰素γ治疗了三种恶性(TGrIII)和两种恶变前(TGrII)尿路上皮细胞系。 (rHu-INF.gamma。)。与未处理的对照相比，用100-1000单位rHu-INF.gamma./ml处理4天后，恶性细胞(HCV29-T112C1、Hu1703He和T24)的生长被抑制超过50％。在rHu-INF.gamma存在的情况下，恶变前细胞系(HCV29和Hu609)的生长没有受到相同程度的影响。在培养基中。用rHu-INF.gamma治疗。正如定量免疫荧光测定所证明的，在所有测试的细胞系中，单形人类白细胞抗原 (HLA) A、B、C 以及 β2-微球蛋白的表达增加。致瘤细胞系以剂量依赖性方式增加其HLA表达，而用较高浓度的rHu-INF.gamma处理非致瘤细胞。超过10单位/ml，不会增加HLA-A、B、C的表达。除非用rHu-INF.gamma处理，否则没有细胞系表达HLAa-DR。致瘤性与rHu-INF.gamma的剂量之间没有相关性。可以证明“从头”诱导 HLA-DR 所需的。去除 rHu-INF.gamma 后。从培养基中观察，HLA-DR 的表达在不到 14 天的时间内逐渐下降，表明 HLA-DR 的表达不是组成型的，而是依赖于 rHu-INF.gamma 的存在。我们得出结论，体外生长的人尿路上皮细胞对 rHu-INF.gamma 的抗增殖和主要组织相容性复合物调节作用敏感，并且恶性尿路上皮细胞比恶性尿路上皮细胞更敏感。癌前细胞。最后，我们的数据表明 rHu-INF.gamma 的可能作用。在人类膀胱癌的治疗中。
In this study we have treated three malignant (TGrIII) and two pre-malignant (TGrII) urothelial cell lines with recombinant human interferon .gamma. (rHu-INF.gamma.). The malignant cells (HCV29-T112C1, Hu1703He and T24) were inhibited in growth by more than 50% after treatment with 100-1000 units of rHu-INF.gamma./ml for 4 days as compared to untreated controls. The growth of the pre-malignant cell lines (HCV29 and Hu609) was not influenced to the same extent in the presence of rHu-INF.gamma. in the culture medium. Treatment with rHu-INF.gamma. increased the expression of monomorphic human leukocyte antigens (HLA) A,B,C as well as .beta.2-microglobulin in all the cell lines tested, as demonstrated using a quantitative immunofluorescence assay. The tumourigenic cell lines increased their expression of HLA in a dose-dependent way, whereas treatment of the non-tumourigenic cells with higher concentrations of rHu-INF.gamma. than 10 units/ml, did not increase the HLA-A,B,C expression. None of the cell lines expressed HLAa-DR unless treated with rHu-INF.gamma.. No correlation between tumourigenicity and the dose of rHu-INF.gamma. required for "de novo" induction of HLA-DR could be demonstrated. After removal of rHu-INF.gamma. from the medium, the expression of HLA-DR gradually decreased in less than 14 days, indicating that the expression of HLA-DR is not constitutive but dependent upon the presence of rHu-INF.gamma.. We conclude that human urothelial cells grown in vitro are sensitive to the anti-proliferative and major-histocompatibility-complex-modulating effects of rHu-INF.gamma., and that malignant urothelial cells are more sensitive than pre-malignant cells. Finally, our data indicate a possible role for rHu-INF.gamma. in the management of human bladder cancer.