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Modulatory effect of progesterone, vitamin D and silibinin on the inflammasomes in monocytes from pegnant women with peeclampsia

Grant number: 15/26147-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2016
Effective date (End): February 28, 2019
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Maria Terezinha Serrão Peraçoli
Grantee:Mariana Leticia Matias
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia (PE) is a specific syndrome of pregnancy, characterized by hypertension and proteinuria, identified after the 20th week of pregnancy. This pathology is associated with hyperuricemia, elevated serum levels of inflammatory cytokines, leukocyte activation and oxidative stress. Uric acid crystals (MSU) and hyalorunan (HA) may activate an intracellular complex called inflammasome, a multi-protein structure which is important for processing and release of inflammatory cytokines such as interleukin-1 beta (IL-1²) and IL-18. The imbalance between pro- and anti-inflammatory cytokines in PE could be dependent on the deficiency of regulatory factors capable of modulating inflammatory response such as vitamin D and progesterone, or this imbalance could be improved by administration of substances with anti-inflammatory properties such as silibinin. The aim of this study is to evaluate the modulatory effect of progesterone, vitamin D and silibinin on NLRP1 and NLRP3 inflammasomes in monocytes from pregnant women with PE and in THP-1 human monocytes cell line. Monocytes obtained from peripheral blood of 20 pregnant women with PE and THP-1 cells will be cultured in the presence or absence of MSU, HA, progesterone, vitamin D or silibinin for different periods: a) 30 min for determination of the NF-kB phosphorylation and analysis of TLR4, IºB and NF-kB expression by flow cytometry, b) 4 h for the gene expression of TLR4, MYD88, NFKB1, NLRP1, NLRP3, CASP1, IL1B, IL18, TNF and IL-10 by RT-qPCR and c) 18 h for the determination of the cytokines concentration by ELISA. Additionally, the culture of THP-1 cells, stimulated or not with MSU, HA, progesterone, vitamin D and silibinin, for 18h will be used to evaluate NLRP1, NLRP3 and caspase-1 proteins by Western blot. The results will be analyzed using non-parametric tests at 5% significance level.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MATIAS, MARIANA LETICIA; ROMAO-VEIGA, MARIANA; RIBEIRO, VANESSA ROCHA; NUNES, PRISCILA REZECK; GOMES, VIRGINIA JULIANI; DEVIDES, AMANDA CARREIRA; BORGES, VERA THEREZINHA; ROMAGNOLI, GRAZIELA GORETTI; PERACOLI, JOSE CARLOS; PERACOLI, MARIA TEREZINHA. Progesterone and vitamin D downregulate the activation of the NLRP1/ NLRP3 inflammasomes and TLR4-MyD88-NF-kappa B pathway in monocytes from pregnant women with preeclampsia. JOURNAL OF REPRODUCTIVE IMMUNOLOGY, v. 144, . (15/26147-3, 16/18155-9)
MATIAS, MARIANA LETICIA; GOMES, VIRGINIA JULIANI; ROMAO-VEIGA, MARIANA; RIBEIRO, VANESSA ROCHA; NUNES, PRISCILA REZECK; ROMAGNOLI, GRAZIELA GORETE; PERACOLI, JOSE CARLOS; SERRAO PERACOLI, MARIA TEREZINHA. Silibinin Downregulates the NF-B Pathway and NLRP1/NLRP3 Inflammasomes in Monocytes from Pregnant Women with Preeclampsia. Molecules, v. 24, n. 8, . (16/18155-9, 16/22854-0, 15/26147-3)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MATIAS, Mariana Leticia. Modulatory effect of progesterone, vitamin D and silibinin on the inflammasomes in monocytes from pregnant women with preeclampsia. 2019. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.

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