INVOLVEMENT OF TNF RECEPTORS IN MONOCYTES POLARIZATION FROM PREGNANT WOMEN WITH PREECLAMPSIA

• Grant number: 24/01285-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date until: August 01, 2024
• End date until: February 28, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• 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: Pre-eclampsia (PE) is a pregnancy-specific syndrome, characterized by an intense systemic inflammatory response, which appears to contribute significantly to the pathophysiology of the disease. Monocytes from the peripheral blood of pregnant women with PE are endogenously activated and polarized towards an inflammatory profile, with an exacerbated production of pro-inflammatory cytokines. The imbalance between pro- and anti-inflammatory cytokines in PE is already well characterized, with a predominance of the concentration of tumor necrosis factor (TNF) over that of Interleukin-10 (IL-10) in plasma and placenta, especially in the most severe cases. of PE and associated with unfavorable maternal outcome. Elevated levels of TNF and its receptors (TNFR1 and TNFR2) have already been described in the plasma of pregnant women with PE. However, the distribution of these receptors in monocytes of pregnant women with PE and their role in the pathogenesis of this important pregnancy syndrome are unknown. In view of this, the determination of these receptors in monocyte subpopulations of pre-eclamptic pregnant women, associated with the plasma concentration of TNF and its soluble receptors, could bring new knowledge to the understanding of the systemic inflammatory response in this pathology.Objectives: 1. To evaluate the involvement of the expression of TNF receptors (TNFR1 and TNFR2) by subpopulations of monocytes in the systemic inflammatory response in pregnant women with pre-eclampsia; 2. Correlate the expression of TNFR1 and TNFR2 by monocytes with the concentration of these soluble receptors and TNF in the plasma of pre-eclamptic pregnant women.Methods: Monocytes obtained from pre-eclamptic pregnant women and normotensive pregnant women (NT) will be evaluated, by flow cytometry, for the expression of the TLR4, CD64, CD163 and CD206 receptors to determine the M1 or M2 profile presented by these cells and the receptors of TNF (TNFR1 and TNFR2). Plasma levels of pro-inflammatory (TNF, IL-1) and anti-inflammatory (IL-10) cytokines and soluble TNF receptors (sTNFR1 and sTNFR2) will be determined using the Elisa technique. The results will be analyzed using parametric or non-parametric tests with a significance level of 5%.