THE DIFFERENTIAL RESPONSE TO INTERFERON-GAMMA BY NORMAL AND TRANSFORMED ENDOTHELIAL-CELLS

Interferon gamma, a multifunctional cytokine secreted by activated T lymphocytes and NK cells, induces normal endothelial cell apoptosis which is inhibited by the activation of protein kinase C. Interestingly, interferon exerts a dual effect on transformed endothelial cell proliferation: at low concentrations it stimulates their growth, while at high concentrations it exerts an inhibitory effect. The different response of normal and transformed endothelial cells correlates with the levels of interferon receptor: when expressed at high levels -such as in normal cells- interferon promotes apoptosis; on the contrary, when cells possess a low number of receptors - such as transformed cells - the cytokine promotes cell growth. Since interferon induces it own receptor, we anticipate that transformed cells exposed to high doses of interferon may upregulate the receptor and, consequently, respond to the cytokine with a reduction in cell viability. (C) 1995 Academic Press, Inc.