title: Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells.
abstract: Cytokines, important biochemical mediators of inflammation, cause a rapid fall in the plasma concentration of cholesterol in vivo. One mechanism by which cytokines may cause acquired hypocholesterolemia is by decreasing the hepatic synthesis and secretion of apolipoproteins. To test this hypothesis, we incubated Hep G2 cells with human recombinant tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. Each of the cytokines resulted in a dose-related reduction in the concentrations of apolipoprotein (apo) A-I, apoB, and lecithin:cholesterol acyltransferase (LCAT) activity in the medium after 24 hours of incubation. The effect of cytokines on apolipoprotein accumulation was not affected by preincubation of Hep G2 cells with fatty acids. Cytokines decreased the concentration of cellular apoA-I mRNA in a dose-related fashion but did not affect cellular concentrations of apoB mRNA. The concentrations of triglyceride and cholesterol were also reduced in the medium of cells incubated with cytokines. Total cell sterol synthesis rates were calculated by [14C]acetate incorporation. Cells incubated with interleukin-6 had a 31% increase in sterol synthesis rate but a 41% decrease in sterol secretion. These data suggest that these cytokines can decrease the hepatic synthesis and/or secretion of apolipoproteins and that this may explain, in part, the acquired hypocholesterolemia seen during acute and chronic inflammation.
authors.affiliation: Department of Internal Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.
authors.forename: W H
authors.initials: WH
authors.lastname: Ettinger
authors.forename: V K
authors.initials: VK
authors.lastname: Varma
authors.forename: M
authors.initials: M
authors.lastname: Sorci-Thomas
authors.forename: J S
authors.initials: JS
authors.lastname: Parks
authors.forename: R C
authors.initials: RC
authors.lastname: Sigmon
authors.forename: T K
authors.initials: TK
authors.lastname: Smith
authors.forename: R B
authors.initials: RB
authors.lastname: Verdery
mesh_terms: D016632:Apolipoprotein A-I / Q000235:genetics; D001053:Apolipoproteins / Q000378:metabolism*; D001055:Apolipoproteins B / Q000235:genetics; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003470:Culture Media; D016207:Cytokines / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001055:Apolipoproteins B; D003470:Culture Media; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008041:Linoleic Acids; D010169:Palmitic Acids; D012333:RNA, Messenger; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D019308:Palmitic Acid; D002784:Cholesterol; D019787:Linoleic Acid; D005954:Glucosephosphate Dehydrogenase; D007862:Phosphatidylcholine-Sterol O-Acyltransferase