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Journal of Lipid Research, Vol. 42, 1636-1644, October 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Regulation of scavenger receptor class B type I in hamster liver and Hep3B cells by endotoxin and cytokines

Correspondence to: Weerapan Khovidhunkit, To whom correspondence should be addressed., wkhovid{at}itsa.ucsf.edu (E-mail)

Multiple changes in HDL metabolism occur during infection and inflammation that could potentially impair the antiatherogenic functions of HDL. Scavenger receptor class B type I (SR-BI) promotes cholesterol efflux from peripheral cells and mediates selective uptake of cholesteryl ester into hepatocytes, thereby playing a pivotal role in reverse cholesterol transport. We studied the effect of endotoxin (lipopolysaccharide, LPS) and cytokines [tumor necrosis factor (TNF) and interleukin 1 (IL-1)] on hepatic SR-BI mRNA and protein levels in Syrian hamsters. LPS significantly decreased SR-BI mRNA levels in hamster liver. This effect was rapid and sustained, and was associated with a decrease in hepatic SR-BI protein levels. High cholesterol diet did not change hepatic SR-BI mRNA levels, and LPS was able to decrease SR-BI mRNA levels during high cholesterol feeding. TNF and IL-1 decreased SR-BI mRNA levels in the liver, and the effects of TNF and IL-1 were additive. TNF and IL-1 also decreased SR-BI levels in Hep3B hepatoma cells. More importantly, TNF and IL-1 decreased the uptake of HDL cholesteryl ester into Hep3B cells. In addition, we studied the effect of LPS on SR-BI mRNA in RAW 264.7 cells, a macrophage cell line. LPS rapidly decreased SR-BI mRNA levels in RAW 264.7 cells, but the effect was not sustained and did not lead to a reduction in SR-BI protein levels.

Our results suggest that the decrease in hepatic SR-BI levels due to LPS and cytokines during infection and inflammation may decrease selective uptake of cholesteryl ester into the liver and result in impaired reverse cholesterol transport. — Khovidhunkit, W., A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold. Regulation of scavenger receptor class B type I in hamster liver and Hep3B cells by endotoxin and cytokines. J. Lipid Res. 2001. 42: 1636–1644.

Supplementary key words: acute-phase response, HDL metabolism, lipopolysaccharide, RAW 264.7 macrophages, reverse cholesterol transport

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