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MODULATORY EFFECT OF MAGNESIUM SULFATE ON NLRP3 INFLAMMASOME EXPRESSION BY HUMAN MONOCYTES STIMULATED IN VITRO WITH MONOSODIUM URATE

Grant number: 22/10669-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2022
Effective date (End): October 31, 2023
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Jose Carlos Peraçoli
Grantee:Gabriela de Oliveira Franco
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Introduction: Evidence in the literature shows that magnesium sulfate (MgSO4) is the medication of choice for the prevention and treatment of eclampsia, in addition to having an anti-inflammatory effect. The anti-inflammatory action of MgSO4 is demonstrated by its inhibitory effect on the production of pro-inflammatory cytokines such as IL-1beta, IL-6, and TNF-alpha in pregnant women with severe preeclampsia. Peripheral blood monocytes of these pregnant women are endogenously activated and express activation of the NLRP3 inflammasome, responsible for the release of inflammatory cytokines, associated with high concentrations of uric acid in the plasma of pregnant women. Objective: To evaluate the modulatory effect of MgSO4 in vitro on the expression of NLRP3 inflammasome and inflammatory cytokines in human monocytes from healthy women, after stimulation of these cells with monosodium urate (MSU). Subjects and methods: 20 healthy, non-pregnant women will be included in the study. Peripheral blood monocytes from these healthy women will be obtained and cultured in vitro in the presence or absence of MSU and MgSO4 for 4h to determine the gene expression of the NLRP3 inflammasome and its components by qPCR and for 18h to determine caspase-1, IL-1beta, IL-18, TNF-alpha and IL-10 by the ELISA technique. The determination of intracellular calcium levels in MgSO4 treated cells will be used to assess whether the effect of magnesium on the NLRP3 inflammasome involves an intracellular calcium-dependent mechanism. The results will be analyzed by parametric or non-parametric tests, with a significance level of 5%.

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