title: Human cholesteryl ester transfer protein expression enhances the mouse survival rate in an experimental systemic inflammation model: a novel role for CETP.
abstract: Mice expressing human cholesteryl ester transfer protein (huCETP) are more resistant to Escherichia coli bacterial wall LPS because death rates 5 days after intraperitoneal inoculation of LPS were higher in wild-type than in huCETP+/+ mice, whereas all huCETP+/+ mice remained alive. After LPS inoculation, plasma concentrations of TNF-alpha and IL-6 increased less in huCETP+/+ than in wild-type mice. LPS in vitro elicited lower TNF-alpha production by CETP expressing than by wild-type macrophages. In addition, TNF-alpha production by RAW 264.7 murine macrophages increased on incubation with LPS but decreased in a dose-dependent manner when human CETP was added to the medium. Human CETP in vitro enhanced the LPS binding to plasma high-density lipoprotein/low-density lipoprotein. The liver uptake of intravenous infused 14C-LPS from Salmonella typhimurium was greater in huCETP+/+ than in wild-type mice. Present data indicate for the first time that CETP is an endogenous component involved in the first line of defense against an exacerbated production of proinflammatory mediators.
authors.affiliation: Lipids Lab (LIM 10), Faculty of Medical Sciences of University of São Paulo, São Paulo, Brazil. lipideq@usp.br
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: Cazita
authors.forename: Denise F
authors.initials: DF
authors.lastname: Barbeiro
authors.forename: Ana I S
authors.initials: AI
authors.lastname: Moretti
authors.forename: Eder C R
authors.initials: EC
authors.lastname: Quintão
authors.forename: Francisco G
authors.initials: FG
authors.lastname: Soriano
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000401:mortality*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012486:Salmonella typhimurium / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha