Altered Kinetics of Tap-1 Gene Expression in Macrophages Following Stimulation with both IFN-γ 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-γ (IFN-γ) 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-γ for 24 hr, suggesting that a posttranscriptional mechanism downregulates TAP gene expression following activation. Treatment of cells with both IFN-γ and lipopolysaccharide (LPS) altered the kinetics and amount of Tap-1 mRNA and protein expression, compared to those with stimulation with IFN-γ alone. These data suggest that LPS enhances the ability of macrophages stimulated with IFN-γ to initiate a cellular immune response by altering the kinetics of TAP gene expression.