title: Regulation of scavenger receptor class B type I in hamster liver and Hep3B cells by endotoxin and cytokines.
abstract: 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.
authors.affiliation: Metabolism Section, Department of Veterans Affairs Medical Center, 4150 Clement Street, Box 111 F, San Francisco, CA 94121, USA. wkhovid@itsa.ucsf.edu
authors.forename: W
authors.initials: W
authors.lastname: Khovidhunkit
authors.forename: A H
authors.initials: AH
authors.lastname: Moser
authors.forename: J K
authors.initials: JK
authors.lastname: Shigenaga
authors.forename: C
authors.initials: C
authors.lastname: Grunfeld
authors.forename: K R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D006224:Cricetinae; D004032:Diet; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D018955:CD36 Antigens; D002788:Cholesterol Esters; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014409:Tumor Necrosis Factor-alpha