Modulation of systemic inflammatory response in preeclampsia

• Grant number: 16/18155-9
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2017 - July 31, 2019
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Maria Terezinha Serrão Peraçoli
• Grantee: Maria Terezinha Serrão Peraçoli
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Jose Carlos Peraçoli ; Mariana Leticia Matias ; Mariana Romão Veiga ; Priscila Rezeck Nunes ; Vanessa Rocha Ribeiro Vasques ; Vera Therezinha Medeiros Borges

Abstract

The literature has been suggesting that the exacerbated systemic inflammatory response detected in pregnant women with preeclampsia (PE) is harmful to the pregnancy progress and may have its origin in placenta. Both innate and adaptive immunity may be involved in this process. Systemic inflammation is a key feature in PE and is represented by excessive concentrations of pro-inflammatory cytokines, associated with reduction of regulatory cytokines and abnormally activated phenotype of cells of innate and adaptive immunity. Thus, both in the systemic circulation and in placenta occur an imbalance between pro-and anti-inflammatory cytokines, activation of NLRP1 and NLRP3 inflammasomes and a polarization of monocytes and T lymphocytes subpopulations to an inflammatory profile, probably dependent on regulatory factors deficiency capable of modulating this inflammatory response. This imbalance could be reduced by the treatment with substances derived from natural products with anti-inflammatory activity, vitamin D and hormones such as progesterone. The present project consisting of four sub-projects has been developed with the objective of evaluating the mechanisms involved in placental and systemic inflammatory responses detected in pregnant women with PE, and to investigate the immunomodulatory effect of hormones such as progesterone, natural products with anti-inflammatory activity such as silybin and vitamin D on monocytes, T cell subsets and placental tissue obtained from preeclamptic women. Thus, the vitro treatment of placental explants and T lymphocytes with vitamin D, and the study of cell signaling pathways in monocytes will allow better understanding of the processes involved in systemic inflammation of PE, and possibly propose alternative ways to treat this important pregnancy syndrome. (AU)

Scientific publications

(10)

(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, APR 2021. (15/26147-3, 16/18155-9)

RIBEIRO, VANESSA ROCHA; ROMAO-VEIGA, MARIANA; NUNES, PRISCILA REZECK; MATIAS, MARIANA LETICIA; PERACOLI, JOSE CARLOS; SERRAO PERACOLI, MARIA TEREZINHA. Vitamin D modulates the transcription factors of T cell subsets to anti-inflammatory and regulatory profiles in preeclampsia. International Immunopharmacology, v. 101, p. 9-pg., 2021-12-01. (16/18155-9, 16/23450-0)

NUNES, PRISCILA R.; ROMAO-VEIGA, MARIANA; MATIAS, MARIANA L.; RIBEIRO, VANESSA R.; DE OLIVEIRA, LEANDRO; PERACOLI, JOSE CARLOS; PERACOLI, MARIA TEREZINHA S.. itamin D decreases expression of NLRP1 and NLRP3 inflammasomes in placental explants from women with preeclampsia cultured with hydrogen peroxid. HUMAN IMMUNOLOGY, v. 83, n. 1, p. 74-80, JAN 2022. (16/18155-9, 16/23452-2)

RIBEIRO, VANESSA ROCHA; ROMAO-VEIGA, MARIANA; NUNES, PRISCILA REZECK; CARDOSO DE OLIVEIRA, LARISSA RAGOZO; ROMAGNOLI, GRAZIELA GORETTI; PERACOLI, JOSE CARLOS; SERRAO PERACOLI, MARIA TEREZINHA. Silibinin downregulates the expression of the Th1 and Th17 profiles by modulation of STATs and transcription factors in pregnant women with preeclampsia. International Immunopharmacology, v. 109, p. 10-pg., 2022-05-06. (16/18155-9, 16/23450-0)

GOMES, VIRGINIA JULIANI; NUNES, PRISCILA REZECK; MATIAS, MARIANA LETICIA; RIBEIRO, VANESSA ROCHA; DEVIDES, AMANDA CARREIRA; BANNWART-CASTRO, CAMILA FERREIRA; ROMAGNOLI, GRAZIELA GORETE; PERACOLI, JOSE CARLOS; SERRAO PERACOLI, MARIA TEREZINHA; ROMAO-VEIGA, MARIANA. Silibinin induces in vitro M2-like phenotype polarization in monocytes from preeclamptic women. International Immunopharmacology, v. 89, p. 9-pg., 2020-12-01. (17/26053-4, 16/18155-9)

GOMES, VIRGINIA JULIANI; NUNES, PRISCILA REZECK; MATIAS, MARIANA LETICIA; RIBEIRO, VANESSA ROCHA; DEVIDES, AMANDA CARREIRA; BANNWART-CASTRO, CAMILA FERREIRA; ROMAGNOLI, GRAZIELA GORETE; PERACOLI, JOSE CARLOS; SERRAO PERACOLI, MARIA TEREZINHA; ROMAO-VEIGA, MARIANA. Silibinin induces in vitro M2-like phenotype polarization in monocytes from preeclamptic women. International Immunopharmacology, v. 89, n. A, DEC 2020. (17/26053-4, 16/18155-9)

NUNES, PRISCILA REZECK; ROMAO-VEIGA, MARIANA; RIBEIRO, VANESSA ROCHA; CARDOSO DE OLIVEIRA, LARISSA RAGOZO; DEPRA, IGOR DE CARVALHO; DE OLIVEIRA, LEANDRO GUSTAVO; PERACOLI, JOSE CARLOS; SERRAO PERACOLI, MARIA TEREZINHA. Inflammasomes in placental explants of women with preeclampsia cultured with monosodium urate may be modulated by vitamin D. HYPERTENSION IN PREGNANCY, v. 41, n. 2, p. 10-pg., 2022-04-11. (16/23452-2, 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, APR 2 2019. (16/18155-9, 16/22854-0, 15/26147-3)

NUNES, PRISCILA REZECK; ROMAO-VEIGA, MARIANA; RIBEIRO, VANESSA ROCHA; DE OLIVEIRA, LARISSA RAGOZO CARDOSO; ZUPELLI, THIAGO GAMEIRO; ABBADE, JOELCIO FRANCISCO; PERACOLI, JOSE CARLOS; PERACOLI, MARIA TEREZINHA SERRAO. Vitamin D decreases cell death and inflammation in human umbilical vein endothelial cells and placental explants from pregnant women with preeclampsia cultured with TNF-alpha. IMMUNOLOGICAL INVESTIGATIONS, DEC 2021. (16/23452-2, 16/18155-9)

ROMAO-VEIGA, MARIANA; RIBEIRO, VANESSA ROCHA; NUNES, PRISCILA REZECK; DE OLIVEIRA, LARISSA RAGOZO CARDOSO; ROMAGNOLI, GRAZIELA GORETTI; PERACOLI, JOSE CARLOS; PERACOLI, MARIA TEREZINHA SERRAO. Immunomodulatory effect of vitamin D on the STATs and transcription factors of CD4(+) T cell subsets in pregnant women with preeclampsia. Clinical Immunology, v. 234, p. 9-pg., 2022-01-05. (16/18155-9, 16/23450-0)