The expression of MHC class II genes in macrophages is cell cycle dependent

Using different drugs, we stopped the cell cycle of bone marrow-derived mac rophages at different points. After IFN-gamma stimulation, macrophages arre sted at the G(1) phase of the cell cycle did not increase cell surface expr ession of the MHC class LI IA, This inhibition is specific, because, under the same conditions, IFN-gamma induces the expression of Fc gamma receptors and the inducible NO synthase mRNA, Treatments that inhibit macrophage pro liferation by blocking the cell cycle at the G(1) phase, such as adenosine, forskolin, or LPS, blocked the IFN-gamma induction of IA, Under IFN-gamma treatment, the steady-state levels of IA alpha and LAP mRNA did not increas e in cells arrested at the G(1) phase and the half-life of the MHC mRNA was not modified. These data suggest that the cell cycle modulation of IFN-gam ma -induced MHC II gene expression occurs at the transcriptional level. The expression of the class II transactivator mRNA induced by IFN-gamma was al so blocked when macrophages were arrested at the G(1) phase of the cell cyc le, suggesting that the lack of IFN-gamma response occurs at the early step s of MHC class II expression, Finally, macrophages arrested at the G(1) pha se showed increased basal levels of cell surface IA due to an increase of t he translational efficiency. These data show that the expression of MHC cla ss II genes is regulated by the cell cycle.