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Human cholesteryl ester transfer protein expression enhances the mouse survival rate in an experimental systemic inflammation model: a novel role for CETP.
- Source :
-
Shock (Augusta, Ga.) [Shock] 2008 Nov; Vol. 30 (5), pp. 590-5. - Publication Year :
- 2008
-
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.
- Subjects :
- Animals
Cells, Cultured
Cholesterol Ester Transfer Proteins genetics
Cholesterol Ester Transfer Proteins pharmacology
Cytokines metabolism
Humans
Interleukin-6 blood
Lipopolysaccharides metabolism
Lipopolysaccharides pharmacokinetics
Lipopolysaccharides pharmacology
Liver drug effects
Liver metabolism
Macrophages metabolism
Mice
Mice, Transgenic
Salmonella typhimurium metabolism
Spleen drug effects
Spleen metabolism
Survival Rate
Tumor Necrosis Factor-alpha blood
Cholesterol Ester Transfer Proteins physiology
Inflammation genetics
Inflammation mortality
Subjects
Details
- Language :
- English
- ISSN :
- 1540-0514
- Volume :
- 30
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Shock (Augusta, Ga.)
- Publication Type :
- Academic Journal
- Accession number :
- 18391856
- Full Text :
- https://doi.org/10.1097/SHK.0b013e31816e30fd