Two distinct pathways of interferon induction as revealed by 2-aminopurine

Activation and repression of IFN gene expression are controlled primarily at the transcriptional level. In order to elucidate some aspects of the induction mechanism of the IFN genes, we examined the effects of different treatments on IFN production in L929 cells, a well-characterized system, and in primary spleen cells. Our results indicate that 2-Aminopurine (2-AP) inhibits type I IFN (IFN-alpha and IFN-beta) induction in L929 cells but not in spleen cells. In L929 cells, 2-AP inhibited the induction of the MuIFN-beta promoter and of promoters containing tetrahexamer and PRDII sequences linked to a reporter gene. Inhibition of activation of the inducible factors binding to the MuIFN-beta promoter and sub-elements was also observed. In contrast, factors binding to the MuIFN-beta promoter are present constitutively in spleen cell nuclei and their activity is not inhibited by 2-AP. These results suggest that 2-AP inhibits IFN-beta gene induction in L929 cells through blocking of activation of the inducible DNA-binding factors which interact with the IFN-beta promoter.