Regulation of scavenger receptor class B type I in hamster liver and Hep3Bcells by endotoxin and cytokines

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.