Study of the NLRP3 participation and of high sodium concentration on macrophage activation by cholesterol crystals

• Grant number: 16/20908-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2017
• End date: January 31, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ronei Luciano Mamoni
• Grantee: Lucas de Souza Loureiro Abbud Santos
• Host Institution: Faculdade de Medicina de Jundiaí (FMJ). Prefeitura Municipal de Jundiaí. Jundiaí , SP, Brazil

Abstract

Atherosclerosis is the main cause of mortality and mobility in the world. Among the risk factors that are associated with its development are high fat and sodium diets. In this way, the formation of the atherosclerosis plaques involves the deposition of lipids in the arterial intima and the activation of an inflammatory response in which macrophages play an important role. The activation of these macrophages depends on the activation and recognition of endogenous substances that were modified, such as cholesterol crystals that were deposited in those plaques and induced the production of inflammatory cytokines. Some studies also have shown that macrophages activation by cholesterol crystals involves the participation of intracellular receptors known as NLRP3 that leads to the production of cytokines such as IL-1² and IL-18. Besides that, some studies indicated that high concentrations of sodium may affect the phenotype of macrophages (directing then from anti-inflammatory M2 to inflammatory M1) and induce the production of other inflammatory cytokines such as IL-6 and TNF-±, in parallel to NLRP3 activation pathway. In this way, this research focus is to investigate the role of NLRP3 in the activation of macrophages, obtained from a THP-1 lineage, by cholesterol crystals and high sodium concentrations. (AU)