Interaction of interferon-gamma and epidermal growth factor in the regulation of nitric oxide production and cellular proliferation in a cultured murine mammary cell line, COMMA-D.

The regulation of nitric oxide synthase (NOS) activity and gene expression by cytokines and growth factors has been studied using the murine mammary epithelial cell line, COMMA-D. NOS activity was stimulated by exposure to interferon-gamma (IFN-gamma) and could be further stimulated by tumour necrosis factor-alpha (TNF-alpha) and epidermal growth factor (EGF) although neither was affective alone. The maximal activity observed in the presence of IFN-gamma and EGF was not affected by the order in which cells were exposed. Messenger RNA levels for the inducible NOS isoform were increased by IFN-gamma and TNF-alpha in a manner consistent with the elevation of NOS activity. EGF also stimulated thymidine incorporation into DNA which was attenuated by coexposure with IFN-gamma in a manner that appeared to be largely NO-independent.