Induction of macrophage Ia antigen expression by rIFN-gamma and down-regulation by IFN-alpha/beta and dexamethasone are regulated transcriptionally.
In previous studies, the induction of Ia Ag on murine macrophages by rIFN-gamma and the antagonism of this induction by IFN-alpha/beta and glucocorticoids were examined. These findings showed that both the induction of Ia Ag by rIFN-gamma, as well as the antagonism of rIFN-gamma-induced Ia Ag expression by IFN-alpha/beta and dexamethasone, are regulated by cognate changes in Ia mRNA. In the present report, this observation was first extended to show that the decreased steady-state level of Ia-specific mRNA seen in the cytoplasm of macrophages treated with rIFN-gamma in the presence of IFN-alpha/beta or dexamethasone were also seen in nuclear RNA preparations. To test the hypothesis that alterations in the rate of Ia gene transcription were responsible for these changes in steady-state levels, nuclear "run on" transcription experiments were performed. The results indicate that both the induction of Ia gene expression by rIFN-gamma and its inhibition by IFN-alpha/beta or dexamethasone are regulated by changes in Ia gene transcription.
Fertsch-Ruggio
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D
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Schoenberg
D R
DR
Vogel
S N
SN
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics*; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D011994:Recombinant Proteins; D012313:RNA; D003907:Dexamethasone; D007371:Interferon-gamma