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Macrophage activation in mice genetically selected for acute inflammatory reaction: evaluation of the SLC11a1 gene role in the macrophage activation during an acute inflammatory response

Grant number: 09/14506-8
Support type:Regular Research Grants
Duration: December 01, 2009 - November 30, 2011
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Nancy Starobinas
Grantee:Nancy Starobinas
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Lines of mice genetically selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory reaction (AIR), present an ability to produce distinct neutrophil influx. These mice have polarized phenotypes in responses against intracellular pathogens and LPS - induced endotoxemic shock. These mice also present distinct susceptibility to tumors development, being the AIRmax animals more resistant than AIRmin mice. In these phenotypes, macrophages are the major effector cells. When present in the tumoral environment, they play an important role in inflammation and tumorigenesis, being source and target of different cytokines, chemokines and signaling molecules. The aim of this work is the characterization of the activity of resident or thioglicollate-induced macrophages in the peritoneal exudate from AIRmax and AIRmin mice. Since Slc11a1 (formerly Nramp1) protein is involved in resistance to infection and it interferes with macrophages activation, oxidative burst, inflammatory cytokines production and nitric oxide (NO) secretion, mouse lines homozygous for resistance and susceptibility Slc11a1 gene alleles (AIRmaxRR, AIRmaxSS, AIRminRR and AIRminSS) were produced in our Lab. This project intends to analyze different macrophages phenotypes, such as pro-inflammatory cytokines production and secretion (IL-1, IL-6, IL-12 and TNFa), as well as anti-inflammatory cytokines (TGF- b e IL-10), NO and H2O2 production inside the inflammatory exudate. These phenotypes will be correlated with different levels of macrophage regulatory genes expression. (AU)