Human cholesteryl ester transfer protein expression enhances the mouse survival rate in an experimental systemic inflammation model: a novel role for CETP.
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.
Cazita
Patrícia M
PM
Lipids Lab (LIM 10), Faculty of Medical Sciences of University of São Paulo, São Paulo, Brazil. lipideq@usp.br
Barbeiro
Denise F
DF
Moretti
Ana I S
AI
Quintão
Eder C R
EC
Soriano
Francisco G
FG
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
D053480:Cholesterol Ester Transfer Proteins; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha