The <i>NLRP3</i> rs10754558 polymorphism is a risk factor for preeclampsia in a Chinese Han population

Xu, Liang; Li, Sai; Liu, Zhen; Jiang, Shanwen; Wang, Jingli; Guo, Ming; Zhao, Xin; Song, Weiqing; Liu, Shiguo

doi:10.1080/14767058.2017.1418313

Cited by 17 publications

(14 citation statements)

References 38 publications

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“…We also demonstrated that preeclamptic placentas show higher expression of NLRP3 inflammasome, which may be involved in the exaggerated inflammatory state seen in this disease [16]. Xu et al also suggested that NLRP3 may be involved in the development of preeclampsia in a Chinese Han population [17].…”

Section: Introductionsupporting

confidence: 57%

Hydrogen peroxide-mediated oxidative stress induces inflammasome activation in term human placental explants

Nunes

Peraçoli

Romao‐Veiga

et al. 2018

Pregnancy Hypertension

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Background: The placenta is a multifunctional organ that can suffer with imbalances between pro-and antioxidant molecules, contributing for inflammatory imbalance. The inflammation generated by oxidative stress may induce inflammasome activation, an essential complex for pro-inflammatory cytokine production. Objective: The aim of this study was to evaluate whether hydrogen peroxide (H 2 O 2) mediated oxidative stress induces inflammasome activation on placental explants. Study design: Tissue cultures of placental explants obtained from normotensive pregnant women were performed in different concentrations of H 2 O 2. Gene expressions of NLRP3, caspase-1, IL-1β, TNF-α and IL-10 were evaluated by qPCR. Superoxide dismutase (SOD), catalase, Heat shock protein 70 (Hsp70), Caspase-1, TNF-α, IL-1β, IL-10 and human Chorionic Gonadotropin (hCG) were determined by ELISA. Results: Concentrations of catalase, Hsp70, hCG and SOD were higher in cultures with 100 and 1000 µM H 2 O 2 compared to controls. Gene and protein expressions of TNF-α and IL-1β were elevated in cultures with 1000 μM H 2 O 2 compared to controls. This concentration led to inflammasome activation, by increasing gene expressions of NLRP3, caspase-1 and IL-1β. In contrast, gene and protein expressions of IL-10 were reduced at 100 and 1000 μM H 2 O 2. Protein expression of caspase-1 was higher in cultures of 100 μM H 2 O 2 compared to controls. Treatment with Glybenclamide at 200 μM was used to prevent NLRP3 inflammasome activation. This concentration reduced protein expression of caspase-1 compared to culture with only H 2 O 2 and control cultures. Conclusions: Our results confirm that H 2 O 2 induces oxidative stress on placental explants and demonstrate that cell responses to this stress involve inflammasome activation.

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Section: Introductionsupporting

confidence: 57%

Hydrogen peroxide-mediated oxidative stress induces inflammasome activation in term human placental explants

Nunes

Peraçoli

Romao‐Veiga

et al. 2018

Pregnancy Hypertension

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“…Mulla et al (107) and Xie et al (101) were the first to demonstrate that NLRP3 inflammasome activation in trophoblasts and peripheral blood was implicated in the pathogenesis of preeclampsia. Indeed, it has been shown that peripheral monocytes from women with preeclampsia display enhanced expression of NLRP1 and NLRP3 (103,266,267), and polymorphisms in their coding genes are associated with the development of this syndrome (268,269). In addition, women with preeclampsia had elevated levels of total cholesterol and uric acid, cellular metabolites that act as alarmins when released extracellularly (270,271), which can potentially activate the NLRP3 inflammasome in the syncytiotrophoblast layer of the placenta (113).…”

Section: Inflammasomes In Pregnancy Complications Associated With Plamentioning

confidence: 99%

Inflammasomes: Their Role in Normal and Complicated Pregnancies

Gomez‐Lopez

Motomura

Miller

et al. 2019

The Journal of Immunology

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Abbreviations used in this article: AIM2, absent in melanoma-2; ASC, apoptosisassociated speck-like protein containing a caspase recruitment domain; DAMP, damage-associated molecule pattern; GSDMD, gasdermin D; NAIP, NLR family apoptosis inhibitory protein; NLR, nucleotide-binding oligomerization domain leucine-rich repeat-containing protein; NLRC4, CARD domain-containing protein-4; NLRP, NLR and pyrin domain-containing protein; PAMP, pathogen-associated molecular pattern; T3SS, type 3 secretion system.

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“…Researchers discovered a significantly higher expression of the NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3), and related mediators such as caspase-1, IL-1β, and IL-18 in samples from women with PE compared to controls [ 3 ]. Moreover, Xu et al and Pontillo et al reported that specific NLRP3 gene polymorphisms are associated with a significantly higher risk of PE development [ 4 , 5 ]. This article aims to delineate the role of NLRP3 in the development of preeclampsia, its symptoms, and complications.…”

Section: Introductionmentioning

confidence: 99%

The NLRP3 Inflammasome Role in the Pathogenesis of Pregnancy Induced Hypertension and Preeclampsia

Socha

Malinowski

Puk

et al. 2020

Cells

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Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of these diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate the crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1β, IL-18, and gasdermin D. Production of these proinflammatory chemokines is the beginning of a local and general inflammation, which results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. The NLRP3 inflammasome is a critical complex in the mediation of the inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Herein, the presented article delineates molecular mechanisms of these processes, indicating directions of future advance.

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The NLRP3 rs10754558 polymorphism is a risk factor for preeclampsia in a Chinese Han population

Abstract: Our results reveal that NLRP3 may be involved in the development of PE in a Chinese Han population. However, further validation of the associations of other NLRP3 SNPs with PE in other populations is required.

Cited by 17 publications

References 38 publications

Hydrogen peroxide-mediated oxidative stress induces inflammasome activation in term human placental explants

Hydrogen peroxide-mediated oxidative stress induces inflammasome activation in term human placental explants

Inflammasomes: Their Role in Normal and Complicated Pregnancies

The NLRP3 Inflammasome Role in the Pathogenesis of Pregnancy Induced Hypertension and Preeclampsia

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