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Mediators of Inflammation
Volume 2016 (2016), Article ID 1784014, 12 pages
http://dx.doi.org/10.1155/2016/1784014
Research Article

CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis

1Lipids Laboratory (LIM 10), Faculty of Medical Sciences, The University of São Paulo, São Paulo, SP, Brazil
2Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Science IV, University of São Paulo, São Paulo, SP, Brazil
3Emergency Care Research Unit Laboratory (LIM 51), Faculty of Medical Sciences, The University of São Paulo, São Paulo, SP, Brazil

Received 1 February 2016; Revised 5 April 2016; Accepted 6 April 2016

Academic Editor: Anshu Agrawal

Copyright © 2016 Tatiana Martins Venancio et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sepsis is a systemic inflammatory response to infection eliciting high mortality rate which is a serious health problem. Despite numerous studies seeking for therapeutic alternatives, the mechanisms involved in this disease remain elusive. In this study we evaluated the influence of cholesteryl ester transfer protein (CETP), a glycoprotein that promotes the transfer of lipids between lipoproteins, on the inflammatory response in mice. Human CETP transgenic mice were compared to control mice (wild type, WT) after polymicrobial sepsis induced by cecal ligation and puncture (CLP), aiming at investigating their survival rate and inflammatory profiles. Macrophages from the peritoneal cavity were stimulated with LPS in the presence or absence of recombinant CETP for phenotypic and functional studies. In comparison to WT mice, CETP mice showed higher survival rate, lower IL-6 plasma concentration, and decreased liver toll-like receptor 4 (TLR4) and acyloxyacyl hydrolase (AOAH) protein. Moreover, macrophages from WT mice to which recombinant human CETP was added decreased LPS uptake, TLR4 expression, NF-κB activation and IL-6 secretion. This raises the possibility for new therapeutic tools in sepsis while suggesting that lowering CETP by pharmacological inhibitors should be inconvenient in the context of sepsis and infectious diseases.