白细胞介素-4受体在艾滋病相关卡波西肉瘤细胞中的表达以及对重组人白细胞介素-4和白细胞介素-4毒素（DAB389-IL-4）的反应
IL-4R expression in AIDS-KS cells and response to rhIL-4 and IL-4 toxin (DAB389-IL-4).
作者信息
Cai J, Zheng T, Murphy J, Waters C A, Lin G Y, Gill P S
机构信息
Department of Medicine, University of Southern California, Los Angeles, USA.
出版信息
Invest New Drugs. 1997;15(4):279-87. doi: 10.1023/a:1005958123893.
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 (IC50 of 5 x 10(-11) M). 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.
白细胞介素-4（IL-4）是一种多效细胞因子，可影响多种细胞类型的生长和分化，并调节其他细胞因子。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中IL-4受体（IL-4R）的表达。KS细胞表达单一的4 kB IL-4R特异性mRNA，每个细胞有1828±408个高亲和力IL-4结合位点，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表达的抑制作用极小。然后，我们研究了一种嵌合融合毒素DAB389-IL-4的作用，该毒素仅对表达IL-4R的细胞产生细胞毒性。DAB389-IL-4在低浓度（IC50为5×10^(-11) M）时可抑制AIDS-KS细胞中的蛋白质合成。这种作用可被抗IL-4中和抗体（25D2）消除。我们得出结论，KS细胞表达功能性IL-4R，该受体可作为DAB389-IL-4等药物新型治疗的靶点。
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