title: Endogenous and Uric Acid-Induced Activation of NLRP3 Inflammasome in Pregnant Women with Preeclampsia.
abstract: Preeclampsia (PE) is a specific syndrome of pregnancy, characterized by hypertension and proteinuria. This pathology is associated with hyperuricemia and elevated serum levels of inflammatory cytokines. Uric acid crystals may activate an intracellular complex called inflammasome, which is important for processing and release of inflammatory cytokines. This study investigated the state of monocyte activation, both endogenous and stimulated with monosodium urate (MSU), by gene expression of NLRP1 and NLRP3 receptors as well as their association with inflammatory cytokines expression. Monocytes were obtained from peripheral blood of 23 preeclamptic pregnant women, 23 normotensive pregnant women (NT) and 23 healthy non-pregnant women (NP). Inflammasome activation was evaluated by the gene expression of NLRP1, NLRP3, caspase-1, IL-1β, IL-18 and TNF-α by RT-qPCR in unstimulated monocytes (endogenous expression), or after cell stimulation with MSU (stimulated expression). The concentration of cytokines was assessed by ELISA. In preeclamptic pregnant women, gene expression of NLRP1, NLRP3, caspase-1, IL-1β and TNF-α by monocytes stimulated or not with MSU was significantly higher than in NT and NP groups. Stimulation of monocytes from preeclamptic and non-pregnant women with MSU induced increased gene expression of NLRP3, caspase-1 and TNF-α in relation to the endogenous expression in these groups, while this was not observed in the NT group. The cytokine determination showed that monocytes from women with PE produced higher endogenous levels of IL-1β, IL-18 and TNF-α compared to the other groups, while the stimulus with MSU led to higher production of these cytokines in preeclamptic group than in the NT group. In conclusion, the results showed increased basal gene expression of NLRP1 and NLRP3 receptors in monocytes from PE group. These cells stimulation with MSU demonstrates that uric acid plays a role in NLRP3 inflammasome activation, suggesting the participation of this inflammatory complex in the pathogenesis of preeclampsia.
authors.affiliation: Department of Gynecology and Obstetrics, Botucatu Medical School, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: Mariana Leticia
authors.initials: ML
authors.lastname: Matias
authors.affiliation: Department of Microbiology and Immunology, Institute of Biosciences, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Romão
authors.affiliation: Department of Microbiology and Immunology, Institute of Biosciences, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: Ingrid Cristina
authors.initials: IC
authors.lastname: Weel
authors.affiliation: Department of Microbiology and Immunology, Institute of Biosciences, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: Vanessa Rocha
authors.initials: VR
authors.lastname: Ribeiro
authors.affiliation: Department of Microbiology and Immunology, Institute of Biosciences, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: Priscila Rezeck
authors.initials: PR
authors.lastname: Nunes
authors.affiliation: Department of Gynecology and Obstetrics, Botucatu Medical School, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: Vera Therezinha
authors.initials: VT
authors.lastname: Borges
authors.affiliation: Department of Microbiology and Immunology, Institute of Biosciences, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: João Pessoa
authors.initials: JP
authors.lastname: Araújo
authors.affiliation: Department of Gynecology and Obstetrics, Botucatu Medical School, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Peraçoli
authors.affiliation: Department of Gynecology and Obstetrics, Botucatu Medical School, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: de Oliveira
authors.affiliation: Department of Microbiology and Immunology, Institute of Biosciences, São Paulo State University, Botucatu, SP, Brazil.
authors.forename: Maria Terezinha
authors.initials: MT
authors.lastname: Peraçoli
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D014527:Uric Acid / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; C427903:NLRP1 protein, human; C453881:NLRP3 protein, human; D014527:Uric Acid; D020170:Caspase 1