PHOSPHOLIPASE-C GAMMA-1 OVEREXPRESSION AND ACTIVATION-INDUCED BY INTERFERON-BETA IN HUMAN T-LYMPHOCYTES - AN ISGF3-INDEPENDENT RESPONSE

Interferons exert their antiviral, antiproliferative and immunoregulat ory activities by stimulating the expression of several genes, Such ge nes disclose a common element within their promoters, defined Interfer on Stimulated Response Element (ISRE), which binds a nuclear factor(s) translocated from the cytoplasm to the nucleus (ISGF3) after the bind ing of interferon (IFN) to the specific receptor, Here we report the i nduction of the synthesis and of the hydrolytic activity of phospholip ase C gamma 1 (PLC gamma 1) in human T lymphocytes by IFN-beta. The in creased level of PLC gamma 1 becomes evident after 90 min of IFN-beta treatment and is still detectable after 24 h. Neither the PLC gamma 1 overexpression induced by IFN nor the increased hydrolytic activity of the enzyme appear to be affected by pretreatment of the cells with th e protein tyrosine kinase inhibitor genistein, which is known to preve nt the association of ISGF3 components, These results suggest that in human T lymphocytes IFN-P can activate other transcription factor(s) d istinct from ISGF3 to regulate PLC yl expression, In addition, the abi lity of this enzyme to hydrolyse PIP2, also in the presence of geniste in, implies the possibility that this enzyme can exert its hydrolytic activity independently of protein tyrosine kinase activation. (C) 1997 Academic Press Limited.