title: Altered kinetics of Tap-1 gene expression in macrophages following stimulation with both IFN-gamma and LPS.
abstract: With recent studies suggesting a key role for professional antigen presenting cells in the induction of major histocompatibility class I cellular immune responses, we initiated studies on the regulation of Tap-1 and Tap-2 gene expression in macrophages. Stimulation of the human macrophage cell line THP-1 with interferon-gamma (IFN-gamma) resulted in maximal induction of both Tap-1 and Tap-2 mRNA within 24 hr. Nuclear run-on analyses showed that the increased expression of Tap-1 and Tap-2 was controlled at the level of transcription. Half-life studies demonstrated that mRNAs for both genes became destabilized after stimulation of THP-1 cells with IFN-gamma for 24 hr, suggesting that a posttranscriptional mechanism down-regulates TAP gene expression following activation. Treatment of cells with both IFN-gamma and lipopolysaccharide (LPS) altered the kinetics and amount of Tap-1 mRNA and protein expression, compared to those with stimulation with IFN-gamma alone. These data suggest that LPS enhances the ability of macrophages stimulated with IFN-gamma to initiate a cellular immune response by altering the kinetics of TAP gene expression.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Cramer
authors.forename: M J
authors.initials: MJ
authors.lastname: Klemsz
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D004357:Drug Synergism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D007371:Interferon-gamma