Puri R K, Leland P
Laboratory of Molecular Tumor Biology, FDA, Bethesda, MD 20892.
Biochem Biophys Res Commun. 1993 Dec 30;197(3):1424-30. doi: 10.1006/bbrc.1993.2636.
We have previously shown that murine solid tumor cells express high affinity IL-4 receptors (IL-4R) which are internalized after binding to ligand. In the present study, we have examined the regulation of IL-4R by TNF. We demonstrate that TNF upregulated the expression of IL-4R on murine MCA-106 sarcoma cells. Maximum upregulation of IL-4R surface expression occurred after 24 h, whereas, maximum elevation in IL-4R mRNA levels was observed after only 4 hours of TNF treatment. This increase in mRNA levels for IL-4R occurred in a dose dependent manner. As little as 0.83 ng/ml of TNF significantly upregulated mRNA levels, whereas maximum effect was obtained with 83 ng/ml TNF. IL-4 receptor density was increased in response to TNF, no effect on IL-4R affinity was observed. Cycloheximide and Actinomycin D treatment decreased the surface expression of IL-4R by 50% in about 2 h and 7 h, respectively, in both TNF treated and untreated cells indicating the half life for the IL-4R protein expression. These studies may help understand the mechanism of cytokine interaction on tumor cells.
我们之前已经表明，鼠实体瘤细胞表达高亲和力的白细胞介素-4受体（IL-4R），该受体在与配体结合后会被内化。在本研究中，我们检测了肿瘤坏死因子（TNF）对IL-4R的调节作用。我们证明，TNF上调了鼠MCA-106肉瘤细胞上IL-4R的表达。IL-4R表面表达的最大上调在24小时后出现，而TNF处理仅4小时后就观察到IL-4R mRNA水平的最大升高。IL-4R mRNA水平的这种增加呈剂量依赖性。低至0.83 ng/ml的TNF就能显著上调mRNA水平，而83 ng/ml的TNF可产生最大效应。TNF刺激后IL-4受体密度增加，未观察到对IL-4R亲和力的影响。在TNF处理和未处理的细胞中，放线菌酮和放线菌素D处理分别在约2小时和7小时内使IL-4R的表面表达降低50%，这表明了IL-4R蛋白表达的半衰期。这些研究可能有助于理解细胞因子在肿瘤细胞上相互作用的机制。
