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

First Author  Panousis CG Year  2001
Journal  J Lipid Res Volume  42
Issue  5 Pages  856-63
PubMed ID  11352993 Mgi Jnum  J:69840
Mgi Id  MGI:2135530 Citation  Panousis CG, et al. (2001) TGF-beta increases cholesterol efflux and ABC-1 expression in macrophage-derived foam cells: opposing the effects of IFN-gamma. J Lipid Res 42(5):856-63
abstractText  The regulation of ATP-binding cassette transporter 1 (ABC-1) expression by cytokines present within the microenvironment of the atheroma may play an important role in determining the impact of reverse cholesterol transport on the atherosclerotic lesion. We recently reported that the macrophage-activating cytokine interferon (IFN)-gamma inhibited both cholesterol efflux and ABC-1 expression. In the present study, we investigated the effects of transforming growth factor (TGF)-beta, a cytokine also apparent within the atheroma, on cholesterol efflux, ABC-1 expression, and its ability to antagonize the inhibitory effects of IFN-gamma. TGF-beta significantly increased cholesterol efflux in macrophage-derived foam cells from apolipoprotein E (apoE) knockout mice, with maximal effects apparent at 300 pg/ml. The increases in efflux occurred without any effect on the passive diffusion component of efflux mediated by beta-cyclodextrin. Furthermore, the increase in cholesterol 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-beta was also demonstrated to inhibit the IFN-gamma-mediated down-regulation of ABC-1. These results further demonstrate the importance of cytokine cross-talk to impact the process of reverse cholesterol transport through a multitude of processes including the regulation of ABC-1.
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