A Molecular Analysis of the Induction of Class II Major Histocompatibility Antigen Expression on Murine Macrophages by Interferon-Gamma and Its Down-Regulation by Interferon-Alpha/Beta and Dexamethasone
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
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Previous studies have shown that the cell surface expression of class II major histocompatibility MHC antigens on murine macrophages Ia antigens is induced by interferon-gamma IFN-gamma and down-regulated by interferon-alphabeta IFN-alphabeta and dexamethasone DEX. The studies described herein were performed in an attempt to examine the molecular mechanisms by which Ia antigens are induced on murine macrophages by recombinant IFN-gamma riFN-gamma and how this induction process is down-regulated by the selected inhibitors, IFN-alphabeta and DEX. Steady-state analysis of total and cytoplasmic RNA revealed that riFN-gamma induced a 5.7- to 6.5-fold increase in levels of Ia e.g., Aa-specific mRNA. Increases in steady-state mRNA for Ab and Ea gene products were also observed in response to riFN-gamma. Maximum accumulation of Aa-specific mRNA occurred 24 hr post-treatment and required the continued presence of riFN-gamma. Induction of Aa-specific mRNA was sensitive to the protein synthesis inhibitor, cycloheximide CHX.
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