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Nucleic Acids Research, 1992, Vol. 20, No. 11 2749-2754
© 1992


MOLECULAR BIOLOGY

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

Luc Daigneault, Allison Haggarty+, Qiang Hua Meng§ and Daniel Skup*

Institut du Cancer de Montreal, 1560 Sherbrooke East, Montreal, Quebec H2L 4M1, Canada

*To whom correspondence should be addressed

Received March 2, 1992. Revised April 22, 1992. Accepted April 22, 1992.

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 1FN-ß) induction in L929 cells but not in spleen cells. In L929 cells, 2-AP inhibited the induction of the MulFN-ß promoter and promoters containing tetrahexamer and PRDII sequences linked to a reporter gene. Inhibition activation of the inducible factors binding to the MuIFN-ß promoter and sub-elements was also observed. In contrast, factors binding to the MuIFN-ß 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-ß gene induction in L929 cells through blocking of activation of the inducible DNA- binding factors which interact with the IFN-ß promoter.


+Present addresses: Montreal General Hospital Research Institute

§Institute de Recherches Cliniques de Montreal, 1560 Sherbrooke East, Montreal. Quebec H2L 4MI. Canada


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