Mouse interferon gamma pretreated hepatocytes conditioned media suppress cytochrome P-450 induction by TCDD in mouse hepatoma cells.

Mouse interferon gamma (IFN-G) markedly suppressed 7-ethoxyresorufin o-deethylase (EROD) activity when added at the same time as TCDD in mouse primary hepatocyte cultures. IFN-G, however, had no effect on EROD induction by TCDD in Hepa-1 cells, a mouse hepatoma cell line, or Hepa-1 cells cocultured with Kupffer cells when added directly to the culture. EROD induction by TCDD in Hepa-1 cells was suppressed when cells were cultured with IFN-G pretreated mouse hepatocytes conditioned media. The magnitude of suppression was related to the dose of IFN-G and the density of hepatocytes used for the preparation of the conditioned media. Treatment of the monoclonal antibody against IFN-G to the conditioned media did not block the suppression of EROD induction. The suppressive effect of IFN-G pretreated hepatocytes conditioned media on EROD induction, however, was blocked when the conditioned media was heated or treated with trypsin. These results suggested that IFN-G pretreated mouse hepatocytes may release a soluble protein factor(s) which suppressed the EROD induction by TCDD in Hepa-1 cells.