TGF-beta increases cholesterol efflux and ABC-1 expression in macrophage-derived foam cells: opposing the effects of IFN-lambda

The regulation of ATP-binding cassette transporter 1 (ABC-1) expression by cytokines present within the microenvironment of the atheroma may play an i mportant role in determining the impact of reverse cholesterol transport on the atherosclerotic lesion. We recently reported that the macrophange-acti vating cytokine interferon (IFN)-gamma inhibited both cholesterol efflux an d ABC-I expression. In the present study, we investigated the effects of tr ansforming growth factor (TGF)-beta, a cytokine also apparent within the at heroma, on cholesterol efflux, ABC-1 expression, and its ability to antagon ize the inhibitory effects of IFN-gamma. TGF-beta significantly increased c holesterol efflux in macrophage-derived foam cells from apolipoprotein E (a poE) knockout mice, with maximal effects apparent at 300 pg/ml. The increas es in efflux occurred without any effect on the passive diffusion component of efflux mediated by P-cyclodextrin, Furthermore, the increase in cholest erol efflux occurred without any changes in free or esterified cholesterol pools and was consistent with an increase in both ABC-1 message and protein . Finally, TGF-P was also demonstrated to inhibit the: IFN-gamma -mediated down-regulation of ABC-1 These results further demonstrate the importance o f cytokine crosstalk to impact the process of reverse cholesterol transport through a multitude of processes including the regulation of ABC-1., - Pan ousis, C. C., G. Evans, and S. H. Zuckerman. TGF-P increases cholesterol ef flux and ABC-I expression in macrophage-derived foam cells: opposing the ef fects of IFN-gamma.