PT  - JOURNAL ARTICLE
AU  - Qiu, Ling O.
AU  - Linder, Mark W.
AU  - Antonino-Green, Deborah M.
AU  - Valdes, Roland
TI  - Suppression of Cytochrome P450 2E1 Promoter Activity by Interferon-γ and Loss of Response Due to the -71G>T Nucleotide Polymorphism of the CYP2E1<sup>*</sup>7B Allele
AID  - 10.1124/jpet.103.057208
DP  - 2004 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 284--288
VI  - 308
IP  - 1
4099  - http://jpet.aspetjournals.org/content/308/1/284.short
4100  - http://jpet.aspetjournals.org/content/308/1/284.full
SO  - J Pharmacol Exp Ther2004 Jan 01; 308
AB  - The CYP2E1*7B allele is defined by two nucleotide sequence polymorphisms, -71G>T and -333T>A. The CYP2E1 promoter sequence flanking the -71G nucleotide is consistent with a γ-interferon activated sequence. Inflammation and interferon (IFN)-γ suppress expression of CYP2E1 in vivo; however, the exact mechanism is not known. The objectives of this study were to determine whether the CYP2E1 promoter is regulated by IFN-γ and to examine the influence of the nucleotide substitutions on this function. Treatment of HepG2 cells with IFN-γ, after transient transfection with a luciferase reporter gene bearing the native CYP2E1 (-71G) promoter sequence resulted, in a dose-dependent reduction of luciferase activity. In contrast, no suppression was observed in cells transfected with the *7B allele promoter (-333A and -71T) nor a CYP2E1 plasmid containing only the -71T polymorphism. These data indicate that IFN-γ suppresses native CYP2E1 promoter activity and that the -71G is critical for this response. The American Society for Pharmacology and Experimental Therapeutics