Analysis of participation of cholesteryl ester transfer protein (CETP) in inflammatory response triggered by LPS and mediated by Toll-like receptor 4 (TLR4) in macrophages

• Grant number: 12/22422-1
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2013
• End date: January 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Patricia Miralda Cazita
• Grantee: Patricia Miralda Cazita
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The cholesteryl ester transfer protein (CETP) is an important component of reverse cholesterol transport. In plasma, CETP is mostly bound to HDL particles, and is considered a key molecule in this lipoprotein metabolism. Due to the structural homology between CETP and lipopolysaccharide binding protein (LBP) which operates in the innate immune response, raised the hypothesis that CETP could act in the inflammatory response. Recently, we demonstrated that human CETP transgenic mice to have reduced mortality in experimental endotoxemia and polymicrobial sepsis. These findings were accompanied by a decrease in cytokine concentrations, the increase in the migration of neutrophils to the site of infection and reduced hepatic expression of TLR4 when compared to wild type mice, that is, which do not express CETP. Knowing that sepsis causes high mortality in ICUs around the world and has limited therapeutic measures, we thought it necessary a thorough study on the possible role of CETP in the inflammatory response. In the hypothesis that CETP may participate in the initial stages of this process, the goal of this research is to determine the role of exogenous and endogenous CETP in their uptake of LPS and TLR4-mediated signaling in cell culture model using mouse peritoneal macrophages. These data are essential to understand the mechanisms involved in the response to LPS justifying the improved survival we found in these animals, as well as establishing new perspectives for the treatment of sepsis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VENANCIO, TATIANA MARTINS; MACHADO, ROBERTA MARCONDES; CASTOLDI, ANGELA; AMANO, MARIANE TAMI; NUNES, VALERIA SUTTI; ROCHA QUINTAO, EDER CARLOS; SARAIVA CAMARA, NIELS OLSEN; SORIANO, FRANCISCO GARCIA; CAZITA, PATRICIA MIRALDA. CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis. Mediators of Inflammation, 2016. (12/22422-1, 11/04302-6)

VENANCIO, TATIANA MARTINS; MACHADO, ROBERTA MARCONDES; CASTOLDI, ANGELA; AMANO, MARIANE TAMI; NUNES, VALERIA SUTTI; ROCHA QUINTAO, EDER CARLOS; SARAIVA CAMARA, NIELS OLSEN; SORIANO, FRANCISCO GARCIA; CAZITA, PATRICIA MIRALDA. CETP Lowers TLR4 Expression Which Attenuates the Inflammatory Response Induced by LPS and Polymicrobial Sepsis. Mediators of Inflammation, v. 2016, p. 12-pg., 2016-01-01. (12/22422-1, 11/04302-6)