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Inflammasome and autophagy involvement in the pathophysiology of preeclampsia


Preeclampsia (PE) is an obstetric pathology which affects between 3% and 8% of pregnancies and is considered as a major cause of morbidity and mortality, both maternal and fetal. The literature suggests that PE is characterized by a state of maladaptive immune tolerance in maternal-fetal interface, determining low uteroplacental blood flow that results in placental hypoxia / ischemia, oxidative stress and fetal growth restriction. High levels of molecular structures associated with stress and cell death, called damage-associated molecular patterns (DAMPS) such as heat shock protein (Hsp70), high mobility group box 1 (HMGB1), hyaluronan ( HA) and uric acid are present in plasma of pregnant women with PE seem to contribute to the pathogenesis of this disease. These DAMPS bind to Toll-like receptors (TLR) and Nod-like (NLR), present in cells of innate immunity, and activate an intracellular complex called inflammassome, important for processing and release interleukin (IL)-1beta and IL-18. These two cytokines are potent inflammatory mediators, important for the activation of the adaptive immune response and may be responsible for T cell differentiation into Th1 and Th17, respectively. Autophagy is a lysosomal degradation pathway that removes protein aggregates and damaged organelles and maintains the cellular integrity. This cellular integrity may be compromised in pregnant women with PE, due to the presence of placental lesions caused by hypoxia / ischemia. Considering that the generation of inflammassome is related to intense inflammatory response, and autophagy may modulate this inflammatory process, contributing to the maintenance of intracellular homeostasis, the objectives of the present study are: 1) to determine the presence of NLRP3 inflammassome and the occurrence of autophagy in placenta of pregnant women with PE; 2) to evaluate the concentration of DAMPS (Hsp70, HMGB1, hyaluronan and uric acid) in plasma of pregnant women with preeclampsia; 3) to assess the endogenous state of activation, or activation-induced by DAMPS (Hsp70, HA and monosodium urate) in monocytes of these patients, by identifying the presence of NLRP3 inflammassome, and its association with IL-1beta, IL-18 and tumor necrosis factor-alpha (TNF-alfa) in these cells; 4) to evaluate the involvement of T cell subpopulations (Th1, Th2, Treg and Th17 ) by analyzing the profile of cytokines and transcription factors produced by these cell subpopulations; 5) to correlate the inflammasome activation with the profile of these T cell subpopulations. (AU)

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Scientific publications (5)
(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)
WEEL, INGRID C.; ROMAO-VEIGA, MARIANA; MATIAS, MARIANA L.; FIORATTI, EDUARDO G.; PERACOLI, JOSE C.; BORGES, VERA T.; ARAUJO, JR., JOAN P.; PERACOLI, MARIA T.. Increased expression of NLRP3 inflammasome in placentas from pregnant women with severe preeclampsia. JOURNAL OF REPRODUCTIVE IMMUNOLOGY, v. 123, p. 40-47, . (12/24697-8)
ROMAO-VEIGA, MARIANA; RIBEIRO, VANESSA ROCHA; MATIAS, MARIANA LETICIA; NUNES, PRISCILA REZECK; ROMAGNOLI, GRAZIELA GORETE; PERACOLI, JOSE CARLOS; SERRAO PERACOLI, MARIA TEREZINHA. AMPs are able to skew CD4(+) T cell subsets and increase the inflammatory profile in pregnant women with preeclampsi. JOURNAL OF REPRODUCTIVE IMMUNOLOGY, v. 149, . (12/24697-8, 13/00534-5)
I.C. WEEL; V.R. RIBEIRO; M. ROMÃO-VEIGA; E.G. FIORATTI; J.C. PERAÇOLI; M.T.S. PERAÇOLI. Down-regulation of autophagy proteins is associated with higher mTOR expression in the placenta of pregnant women with preeclampsia. Brazilian Journal of Medical and Biological Research, v. 55, . (13/03872-9, 13/00535-1, 12/24697-8)
RIBEIRO, VANESSA R.; ROMAO-VEIGA, MARIANA; ROMAGNOLI, GRAZIELA G.; MATIAS, MARIANA L.; NUNES, PRISCILA R.; BORGES, VERA THEREZINHA M.; PERACOLI, JOSE C.; PERACOLI, MARIA TEREZINHA S.. Association between cytokine profile and transcription factors produced by T-cell subsets in early- and late-onset pre-eclampsia. IMMUNOLOGY, v. 152, n. 1, p. 163-173, . (12/24697-8, 14/25124-7)
ROMAO-VEIGA, MARIANA; MATIAS, MARIANA LETICIA; RIBEIRO, VANESSA ROCHA; NUNES, PRISCILA REZECK; BORGES, VERA THEREZINHA M.; PERACOLI, JOSE CARLOS; PERACOLI, MARIA TEREZINHA S.. Induction of systemic inflammation by hyaluronan and hsp70 in women with pre-eclampsia. CYTOKINE, v. 105, p. 23-31, . (13/00534-5, 12/24697-8)

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