TGF-beta 1 Up-Regulates Expression of ABCA1, ABCG1 and SR-BI through Liver X Receptor a Signaling Pathway in THP-1 Macrophage-Derived Foam Cells

Aim: High density lipoprotein (HDL) and its apolipoproteins can promote cholesterol efflux from macrophage foam cells via the ATP-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B type. (SR-BI). Liver X receptors (LXRs) operate as cholesterol sensors which may protect from cholesterol overload by stimulating cholesterol efflux from cells to HDL through ABCA1, ABCG1 and SR-BI. The regulation of ABCA1, ABCG1 and SR-BI 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. In the current study, we examined the effect of transforming growth factor-alpha 1 (TGF-alpha 1) on expressions of ABCA1, ABCG1 and SR-BI and explored the role of LXR alpha in the regulation of ABCA1, ABCG1 and SR-BI in THP-1 macrophage-derived foam cells. Methods and Results: TGF-alpha 1 significantly increased expressions of ABCA1, ABCG1 and SR-BI at both transcriptional and translational levels in a dose-dependent and time-dependent manner. Cellular cholesterol content was decreased while cholesterol efflux was increased by TGF-alpha 1 treatment. Moreover, LXR alpha was up-regulated by TGF-alpha 1 treatment. In addition, LXR alpha small interfering RNA completely abolished the promotion effect induced by TGF-alpha 1. Conclusion: These results provide evidence that TGF-alpha 1 up-regulates expressions of ABCA1, ABCG1 and SR-BI through the LXR alpha pathway in THP-1 macrophage-derived foam cells.