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Journal of Lipid Research, Vol. 42, 856-863, May 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

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

Correspondence to: Steven H. Zuckerman, To whom correspondence should be addressed., Zuckerman_Steven{at}Lilly.com (E-mail)

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)- inhibited both cholesterol efflux and ABC-1 expression. In the present study, we investigated the effects of transforming growth factor (TGF)-ß, a cytokine also apparent within the atheroma, on cholesterol efflux, ABC-1 expression, and its ability to antagonize the inhibitory effects of IFN-. TGF-ß 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 ß-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-ß was also demonstrated to inhibit the IFN--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. — Panousis, C. G., G. Evans, and S. H. Zuckerman. TGF-ß increases cholesterol efflux and ABC-1 expression in macrophage-derived foam cells: opposing the effects of IFN-. J. Lipid Res. 2001. 42: 856;–863.

Supplementary key words: inflammation, reverse cholesterol transport, apoA-I, cytokines

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