@article {Qiu284, author = {Ling O. Qiu and Mark W. Linder and Deborah M. Antonino-Green and Roland Valdes, Jr.}, title = {Suppression of Cytochrome P450 2E1 Promoter Activity by Interferon-γ and Loss of Response Due to the -71G>T Nucleotide Polymorphism of the CYP2E1*7B Allele}, volume = {308}, number = {1}, pages = {284--288}, year = {2004}, doi = {10.1124/jpet.103.057208}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/308/1/284}, eprint = {https://jpet.aspetjournals.org/content/308/1/284.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }