Interferon-gamma (IFN-gamma) down-regulates receptors associated with reverse cholesterol transport including ABCAL In the present study, the kinetics and mechanism of ABCAl down-regulation were determined in mouse peritoneal macrophages. IFN-gamma decreased ABCAl mRNA 1 h following IFN-gamma addition and was maximally reduced by 3 h. Down-regulation was protein synthesis dependent and involved post-transcriptional processes. ABCAl 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 ABCAl protein, significant 3 h following IFN-gamma addition. The kinetics of ABCAl message and protein decrease was consistent with the early IFN-gamma-induced changes in Statl phosphorylation and nuclear translocation observed in these cells. Therefore, ABCAl can be considered as an early response gene to macrophage activation by IFN-gamma with down-regulation occurring by message destabilization. (c) 2005 Elsevier Inc. All rights reserved.