Both type I and type II interferons down‐regulate human tumor necrosis factor receptors in human hepatocellular carcinoma cell line Hep G2

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Abstract
It is well known that Interferon‐γ (IFN‐γ type II) potentiates various responses of human tumor necrosis factor (TNF) in a wide variety of cells and that this potentiation is accompanied by the up‐regulation of TNF receptor synthesis. In the present studies we examined the regulation of TNF receptors by type I and type II IFNs in a hepatocellular carcinoma cell line, HEP G2. Exposure of these cells to IFN‐γ led to a decrease in TNF receptor number (4029 vs. 2719 sites/cell) without any change in the receptor affinity (0.96 nM vs. 1.1 nM). The effect was time and dose‐dependent. Like IFN‐γ, IFN‐α and IFN‐β (type I) down‐modulated the TNF receptors on these cells. The effect of IFNs on the TNF receptors was inhibited by staurosporin, a protein kinase C (PK‐C) inhibitor. Furthermore, by the use of receptor‐specific antibodies, we found that the IFN‐dependent decrease was primarily due to the p60 form of the TNF receptor. Our results presented are the first to demonstrate that IFNs can also down‐modulate TNF receptors in certain cells and that this effect is mediated through PK‐C.