RESUMO
Interferon-gamma (IFN-gamma) down-regulates receptors associated with reverse cholesterol transport including ABCA1. In the present study, the kinetics and mechanism of ABCA1 down-regulation were determined in mouse peritoneal macrophages. IFN-gamma decreased ABCA1 mRNA 1h following IFN-gamma addition and was maximally reduced by 3h. Down-regulation was protein synthesis dependent and involved post-transcriptional processes. ABCA1 message had a T(1/2) of 115 min in actinomycin treated cells that was reduced to a T(1/2) of 37 min by IFN-gamma. The decrease in message stability was also associated with a rapid loss of ABCA1 protein, significant 3h following IFN-gamma addition. The kinetics of ABCA1 message and protein decrease was consistent with the early IFN-gamma-induced changes in Stat1 phosphorylation and nuclear translocation observed in these cells. Therefore, ABCA1 can be considered as an early response gene to macrophage activation by IFN-gamma with down-regulation occurring by message destabilization.
