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

FEBS Letters

Aggarwal, Bharat B.¹  Pandita, Raj¹ 

[1] Cytokine Research Laboratory, Department of Clinical Immunology and Biological Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA

关键词: Tumor necrosis factor;    Interferon;    TNF receptor;    Protein kinase;    TNF;    tumor necrosis factor;    IFN;    interferon;    p60;    also referred to as p55;    TNF receptor I;    or TNF receptor type B;    p80;    also referred to as p75;    TNF receptor II;    or TNF receptor type A;    FCS;    fetal calf serum;    PK-C;    protein kinase C;   

DOI  :  10.1016/0014-5793(94)80637-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown