W. Khovidhunkit et al., Regulation of scavenger receptor class B type I in hamster liver and Hep3Bcells by endotoxin and cytokines, J LIPID RES, 42(10), 2001, pp. 1636-1644
Multiple changes in HDL metabolism occur during infection and inflammation
that could potentially impair the antiatherogenic functions of HDL. Scaveng
er receptor class B type I (SR-BI) promotes cholesterol efflux from periphe
ral cells and mediates selective uptake of cholesteryl ester into hepatocyt
es, thereby playing a pivotal role in reverse cholesterol transport. We stu
died 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 l
evels in hamster liver. This effect was rapid and sustained, and was associ
ated with a decrease in hepatic SR-Bl 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-B
l 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 impo
rtantly, TNF and IL-1 decreased the uptake of HDL cholesteryl ester into He
p3B cells. In addition, we studied the effect of LPS on SR-BI mRNA in RAW 2
64.7 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. (jlr) Our results suggest that the decr
ease in hepatic SR-BI levels due to LPS and cytokines during infection and
inflammation may decrease selective uptake of cholesteryl ester into the li
ver and result in impaired reverse cholesterol transport.