Intra-amniotic inflammation induces preterm birth by activating the NLRP3 inflammasome†

Faro, Jonathan; Romero, Roberto; Schwenkel, George; Garcia‐Flores, Valeria; Arenas‐Hernandez, Marcia; Leng, Yaozhu; Xu, Yi; Miller, Derek; Hassan, Sonia S.; Gomez‐Lopez, Nardhy

doi:10.1093/biolre/ioy261

Cited by 92 publications

(74 citation statements)

References 181 publications

(247 reference statements)

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“…In a nonprimate rhesus macaques chorioamnionitis model induced by intra-amniotic injection of LPS, the amnion upregulated neutrophil accumulation via the chemoattractant IL-8 in an IL-1-dependent manner (169). In a mouse model of intra-amniotic inflammation-induced preterm birth, the NLRP3 inflammasome was activated following IL-1β secretion in the fetal membranes and decidua basalis (170). In addition, IL-1β blockade decreased inflammation-induced preterm labor in mice (171).…”

Section: Other Pregnancy Complications Associated With the Nlrp3 Inflmentioning

confidence: 99%

Role of the NLRP3 Inflammasome in Preeclampsia

2020

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Reproduction involves tightly regulated series of events and the immune system is involved in an array of reproductive processes. Disruption of well-controlled immune functions leads to infertility, placental inflammation, and numerous pregnancy complications, including preeclampsia (PE). Inflammasomes are involved in the process of pathogen clearance and sterile inflammation. They are large multi-protein complexes that are located in the cytosol and play key roles in the production of the pivotal inflammatory cytokines, interleukin (IL)-1β and IL-18, and pyroptosis. The nucleotide-binding oligomerization domain, leucine-rich repeat-, and pyrin domaincontaining 3 (NLRP3) inflammasome is a key mediator of sterile inflammation induced by various types of damage-associated molecular patterns (DAMPs). Recent evidence indicates that the NLRP3 inflammasome is involved in pregnancy dysfunction, including PE. Many DAMPs (uric acid, palmitic acid, high-mobility group box 1, advanced glycation end products, extracellular vesicles, cell-free DNA, and free fatty acids) are increased and associated with pregnancy complications, especially PE. This review focuses on the role of the NLRP3 inflammasome in the pathophysiology of PE.

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Section: Other Pregnancy Complications Associated With the Nlrp3 Inflmentioning

confidence: 99%

Role of the NLRP3 Inflammasome in Preeclampsia

2020

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“…The mechanisms that lead to sterile intra-amniotic inflammation in preterm [46][47][48][49][50] and term [46,[51][52][53][54] labor implicate inflammasomes, which are cytoplasmic high-molecular-weight multisubunit protein complexes that upon assembly induce the activation of caspase-1 [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73] and the consequent release of mature IL-1β and/or IL-18 [74][75][76][77][78][79][80][81][82]. Accordingly, alarmins (e.g.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the NLRP3 inflammasome can prevent sterile intra-amniotic inflammation, preterm labor/birth, and adverse neonatal outcomes†

Gomez‐Lopez

Romero²,

Garcia‐Flores

et al. 2018

Biology of Reproduction

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Sterile intra-amniotic inflammation is commonly observed in patients with spontaneous preterm labor, a syndrome that commonly precedes preterm birth, the leading cause of perinatal morbidity and mortality worldwide. However, the mechanisms leading to sterile intra-amniotic inflammation are poorly understood and no treatment exists for this clinical condition. Herein, we investigated whether the alarmin S100B could induce sterile intra-amniotic inflammation by activating the NLRP3 inflammasome, and whether the inhibition of this pathway could prevent preterm labor/birth and adverse neonatal outcomes. We found that the ultrasound-guided intra-amniotic administration of S100B induced a 50% rate of preterm labor/birth and a high rate of neonatal mortality (59.7%) without altering the fetal and placental weights. Using a multiplex cytokine array and immunoblotting, we reported that S100B caused a proinflammatory response in the amniotic cavity and induced the activation of the NLRP3 inflammasome in the fetal membranes, indicated by the upregulation of the NLRP3 protein and increased release of active caspase-1 and mature IL-1β.

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“…An in vivo study showed that IL-1β mRNA expression is increased in mouse fetal membranes following LPS stimulation (45). Interleukin 1β transcript expression is also increased in term human fetal membranes explants treated with LPS (95).…”

Section: Discussionmentioning

confidence: 99%

Human Amnion Epithelial Cells (AECs) Respond to the FSL-1 Lipopeptide by Engaging the NLRP7 Inflammasome

et al. 2020

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Context and Objectives: Inflammation is the leading mechanism involved in both physiological and pathological rupture of fetal membranes. Our aim was to obtain a better characterization of the inflammasome-dependent inflammation processes in these tissues, with a particular focus on the nucleotide-binding oligomerization domain (NOD)-like receptor, pyrin domain containing protein 7 (NLRP7) inflammasome. Methods: The presence of NLRP7 inflammasome actors [NLRP7, apoptosis-associated speck-like protein containing a CARD domain (ASC), and caspase-1] was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in human amnion and choriodecidua at the three trimesters and at term. The protein concentrations were then determined by enzyme-linked immunosorbent assay in term tissues, with or without labor. The presence of Mycoplasma salivarium and Mycoplasma fermentans in human fetal membranes was investigated using a PCR approach. Human amnion epithelial cells (AECs) were treated for 4 or 20 h with fibroblast-stimulating lipopeptide-1 (FSL-1), a M. salivarium-derived ligand. Transcripts and proteins quantity was then measured by RT-quantitative PCR and Western blotting, respectively. NLRP7 and ASC colocalization was confirmed by immunofluorescence. Western blots allowed analysis of pro-caspase-1 and gasdermin D cleavage. Results: NLRP7, ASC, and caspase-1 transcripts were expressed in both sheets of human fetal membranes during all pregnancy stages, but only ASC protein expression was increased with labor. In addition, M. salivarium and M. fermentans were detected for the first time in human fetal membranes. NLRP7 and caspase-1 transcripts, as well as NLRP7, ASC, and pro-caspase-1 protein levels, were increased in FSL-1-treated AECs. The NLRP7 inflammasome assembled around the nucleus, and pro-caspase-1 and gasdermin D were cleaved into their mature forms after FSL-1 stimulation. Conclusion: Two new mycoplasmas, M. salivarium and M. fermentans, were identified in human fetal membranes, and a lipopeptide derived from M. salivarium was found to induce NLRP7 inflammasome formation in AECs.

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Intra-amniotic inflammation induces preterm birth by activating the NLRP3 inflammasome†

Cited by 92 publications

References 181 publications

Role of the NLRP3 Inflammasome in Preeclampsia

Role of the NLRP3 Inflammasome in Preeclampsia

Inhibition of the NLRP3 inflammasome can prevent sterile intra-amniotic inflammation, preterm labor/birth, and adverse neonatal outcomes†

Human Amnion Epithelial Cells (AECs) Respond to the FSL-1 Lipopeptide by Engaging the NLRP7 Inflammasome

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