Post-transcriptional regulation of macrophage ABCA1, an early response gene to IFN-gamma.
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.
Alfaro Leon
Martha Leticia
ML
Ciencias Biologicas Program, Universidad Autonoma Metropolitana-Xochimilco, Mexico.
Evans
Glenn F
GF
Farmen
Mark W
MW
Zuckerman
Steven H
SH
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000008:administration & dosage*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000276:immunology*
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D007371:Interferon-gamma