Tumor necrosis factor upregulates interleukin-4 receptors on murine sarcoma cells

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.