Cai J, Zheng T, Murphy J, Waters C A, Lin G Y, Gill P S
Department of Medicine, University of Southern California, Los Angeles, USA.
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。
