Inhibitory effect of interferon-gamma-dependent induction of major histocompatibility complex class II antigen by expressing exogenous poly(ADP-ribose) synthetase gene

Ia antigen, one of class II major histocompatibility complexes, was induced by treatment of mouse macrophage P388D1 cells with interferon-gamma. During the process, expression of poly(ADP-ribose) synthetase gene was depressed. We examined whether or not down-regulation of the synthetase was required for the interferon-gamma-dependent induction of Ia antigen. We constructed expression plasmid harboring metallothionein promoter-regulated synthetase gene. The enzyme activity and mRNA level of the synthetase were increased in exogenous synthetase gene-transfected clones. Induction of Ia antigen gene was strongly inhibited by expressing the exogenous synthetase gene upon treatment of the transfected clones with interferon-gamma. The result suggests that interferon-gamma-dependent down-regulation of the synthetase may be involved in a step of the signal transduction to induce Ia antigen.