Regulation of Interferon Production by Dibutyryl Cyclic GMP in Serum-Free Human Diploid Cell Cultures

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Abstract
The mechanism for regulating interferon production was investigated in relation to accentuation of production in serum-free human diploid cells (strain WI-38) treated with N2,O2-dibutyryl guanosine 3',5'-cyclic monophosphate (db-cyclic GMP). Interferon production in serum-free WI-38 cell cultures in response to Newcastle disease virus (NDV) was greatly reduced. In these cells, there was decreased incorporation of 5-3H-uridine into the acid-insoluble fraction, but unimpaired incorporation of U-14C-L-leucine, as compared with serum-containing cultures. When serum-free cell cultures were treated with 0.2 mM-db-cyclic GMP, incorporation of both 5-3H-uridine and U-14C-L-leucine was increased and there was an 8-fold enhancement in the yield of interferon in response to NDV. Induction of db-cyclic GMP-treated cells by NDV in the presence of cycloheximide and actinomycin D suggests that db-cyclic GMP enhances transcription of the interferon gene, and thereby augments interferon production.

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