Association between gene expression in monocytes and plasma concentration of ADAM17, tumor necrosis factor receptors, and cytokines in pregnant women with preeclampsia.

• Grant number: 25/08430-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Maria Terezinha Serrão Peraçoli
• Grantee: Eduardo Fabricio Seidel
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Introduction: Preeclampsia (PE) is a pregnancy-specific syndrome characterized by elevated serum levels of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-¿), which plays a significant role in the pathophysiology of the disease. This cytokine is primarily produced by innate immune cells (monocytes and macrophages), which are activated in pregnant women with PE and may promote an immune response shift toward a pro-inflammatory profile. TNF-¿ exerts various functional effects on immune cells through its interaction with specific receptors, TNFR1 and TNFR2. Interaction with TNFR1 induces pro-inflammatory effects, while engagement with TNFR2 elicits anti-inflammatory responses, including the upregulation of IL-10 production. TNF-¿, TNFR1, and TNFR2 can undergo proteolytic cleavage from the plasma membrane by the TNF-¿ converting enzyme (ADAM17/TACE), resulting in the release of their soluble forms into the plasma. Although the role of this metalloproteinase in the cleavage of membrane-bound TNF-¿ from innate immune cells is known, no studies have compared plasma concentrations of ADAM17 and TNF receptors between women with PE and normotensive pregnant women. Objectives: 1. To evaluate the gene expression of the metalloproteinase ADAM17, TNF receptors (TNFR1 and TNFR2), and cytokines (TNF-¿ and IL-10) in monocytes from pregnant women with PE and normotensive pregnant women. 2.To determine the plasma concentrations of TNF-¿, IL-10, soluble TNF receptors (sTNFR1 and sTNFR2), and the enzyme ADAM17 in these individuals. Subjects and Methods: The study will include 20 pregnant women diagnosed with isolated PE and 20 gestational age-matched normotensive pregnant women. The endogenous gene expression of TNF-¿, IL-10, ADAM17, TNFR1, and TNFR2 in monocytes will be assessed using RT-qPCR. Plasma concentrations of TNF-¿, IL-10, sTNFR1, sTNFR2, and ADAM17 will be measured by ELISA. Data will be analyzed using non-parametric statistical tests, with a significance level of 5%. (AU)