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Polarization of THP-1 cells to M1/M2 profiles induced by HMGB1 and silibinin

Grant number: 16/22950-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2017
Effective date (End): December 31, 2018
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Maria Terezinha Serrão Peraçoli
Grantee:Mariane Font Fernandes
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia is a gestational specific syndrome characterized by a maladaptation state of the immunological tolerance, identified by oxidative stress and abnormal activation of the innate immune system. In plasma of pregnant women with PE there are elevated levels of molecular structures associated with stress and cell death, called damage-associated molecular patterns (DAMPs) such as High mobility group box 1 (HMGB1) which appear to contribute directly to the pathogenesis of this disease. These DAMPs can activate monocytes switching them to the M1 profile. The imbalance between pro- and anti-inflammatory cytokines in the PE could be improved by administration of silibinin, a flavonoid with anti-inflammatory properties. The aim of this work is to modulate cells of monocytic lineage (THP-1) to pro - (M1) and anti-inflammatory (M2) profiles using HMGB1 and silibinin in order to understand the activation pathways of monocytes in PE. THP-1 cells will be cultured with or without HMGB1 or silibinin for 18 h for analysis of TLR4, RAGE, CD64, CD163 and CD14 receptors expression by flow cytometry and for the determination of the concentration of the cytokines IL-1², IL-6, IL-8, IL-10, IL-12p70 and TNF-± by CBA. The results will be analyzed using parametric or nonparametric tests with 5% of significance level. (AU)