title: Lipopolysaccharide down regulates both scavenger receptor B1 and ATP binding cassette transporter A1 in RAW cells.
abstract: Lipopolysaccharide (LPS) has recently been shown to facilitate macrophage foam cell formation and has been suggested to be a proatherogenic factor. The mechanism of LPS induced cholesterol accumulation, however, is unclear. In this report, using the macrophage-like RAW 264.7 cell line, we provide experimental evidence that LPS's proatherogenic effects may at least in part reflect altered cholesterol metabolism. Data presented demonstrate that in a dose-dependent manner, LPS is able to down regulate the mRNA expression of the two primary high-density lipoprotein (HDL) receptors, scavenger receptor B1 (SR-B1) and ATP binding cassette A1 (ABCA1), with a 50% inhibitory concentration of less than 0.2 ng/ml, as well as to decrease SR-B1 protein expression by 80%. We also found that LPS treatment resulted in a significant decrease (to 20% of the control level) of the specific (125)I-HDL binding as well as in 50% inhibition of the HDL-mediated cholesterol efflux compared to untreated cells. In addition, we compared the potencies of various modified LPS preparations and demonstrated that the phosphorylated lipid A portion of LPS, which is highly conserved among gram-negative microorganisms, including Chlamydia, is primarily responsible for the effects of LPS on SR-B1 and ABCA1 expression. Inhibitors of NF-kappaB activation were observed to efficiently block the suppressive effect of LPS on SR-B1 and ABCA1, suggesting a mechanism involving NF-kappaB. These data indicate that the LPS effects on cholesterol metabolism may contribute to the proatherogenic properties of LPS.
authors: National Heart, Lung and Blood Institute, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 20892, USA.
authors: Irina
authors: I
authors: Baranova
authors: Tatyana
authors: T
authors: Vishnyakova
authors: Alexander
authors: A
authors: Bocharov
authors: Zhigang
authors: Z
authors: Chen
authors: Alan T
authors: AT
authors: Remaley
authors: John
authors: J
authors: Stonik
authors: Thomas L
authors: TL
authors: Eggerman
authors: Amy P
authors: AP
authors: Patterson
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008565:Membrane Proteins; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013997:Time Factors; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014108:Tosylphenylalanyl Chloromethyl Ketone; D002784:Cholesterol