IL-4R expression in AIDS-KS cells and response to rhIL-4 and IL-4 toxin (DAB389-IL-4).

IL-4R expression in AIDS-KS cells and response to rhIL-4 and IL-4 toxin (DAB389-IL-4).
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AIDS-KS 细胞中的 IL-4R 表达以及对 rhIL-4 和 IL-4 毒素 (DAB389-IL-4) 的反应。

DOI:
10.1023/a:1005958123893
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发表时间:
1997
影响因子:
3.4
通讯作者:
Gill,PS
Gill,PS
中科院分区:
医学3区
文献类型:
--
作者:
Cai,J;Zheng,T;Murphy,J;Waters,CA;Lin,GY;Gill,PS

文献摘要

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白细胞介素-4(IL-4)是一种多效性细胞因子,影响各种细胞类型的生长和分化以及调节其他细胞因子。为了研究IL-4对艾滋病相关卡波西肉瘤(AIDS-KS)细胞的作用,我们首先检测了肿瘤细胞的IL-4受体(IL-4 R)表达。KS细胞表达单个4 kB IL-4 R特异性mRNA和1828 ± 408个高亲和力IL-4结合位点/细胞,解离常数(Kd)为154 ± 37 pM。添加重组人IL-4(rIL-4)对AIDS-KS细胞生长和IL-6表达的抑制作用最小。然后,我们研究了嵌合融合毒素DAB 389-IL-4的作用,其仅对表达IL-4 R的细胞产生细胞毒性。在低浓度下,DAB 389-IL-4抑制AIDS-KS细胞蛋白质合成(IC_(50))为5 × 10 ~(-11)M。这种作用被IL-4中和抗体(25 D2)消除。我们得出结论,KS细胞表达功能性IL-4 R,这种受体可以作为新的治疗药物,如DAB 389-IL-4的目标。
Interleukin-4 (IL-4) is a pleiotropic cytokine affecting growth and differentiation of various cell types as well as regulating other cytokines. To study the effect of IL-4 on AIDS-related Kaposi's sarcoma (AIDS-KS) cells, we first examined the tumor cells for IL-4 receptor (IL-4R) expression. KS cells express a single 4 kB IL-4R-specific mRNA and 1828 ± 408 high affinity IL-4 binding sites per cell with a dissociation constant (Kd) of 154 ± 37 pM. Addition of recombinant human IL-4 (rIL-4) minimally inhibited AIDS-KS cell growth and expression of IL-6. We then studied the effects of a chimeric fusion toxin DAB389-IL-4 which exerts cellular toxicity only on cells expressing IL-4R. DAB389-IL-4 inhibited protein synthesis in AIDS-KS cells at low concentrations (IC50of 5 × 10-11M). This effect was abrogated by neutralizing antibody to IL-4 (25D2). We conclude that KS cells express a functional IL-4R and this receptor could serve as a target for novel therapy with agents such as DAB389-IL-4.