scholarly journals Maternal extracellular vesicles and platelets promote preeclampsia via inflammasome activation in trophoblasts

Blood ◽  
2016 ◽  
Vol 128 (17) ◽  
pp. 2153-2164 ◽  
Author(s):  
Shrey Kohli ◽  
Satish Ranjan ◽  
Juliane Hoffmann ◽  
Muhammed Kashif ◽  
Evelyn A. Daniel ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Nlrp3 Inflammasome ◽  
Purinergic Signaling ◽  
Atp Release ◽  
Inflammasome Activation ◽  
Trophoblast Cells ◽  
Nlrp3 Inflammasome Activation ◽  
Key Points

Key Points EVs cause accumulation of activated maternal platelets within the placenta, resulting in a thromboinflammatory response and PE. Activated maternal platelets cause NLRP3-inflammasome activation in trophoblast cells via ATP release and purinergic signaling.

scholarly journals Placental thrombo-inflammation impairs embryonic survival by reducing placental thrombomodulin expression

Blood ◽  
2020 ◽  
Author(s):  
Shrey Kohli ◽  
Kunal Kumar Singh ◽  
Anubhuti Gupta ◽  
Paulina Markmeyer ◽  
Franziska Lochmann ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Extracellular Vesicles ◽  
Platelet Activation ◽  
Nlrp3 Inflammasome ◽  
Pregnancy Complications ◽  
Embryonic Lethality ◽  
Inflammasome Activation ◽  
Embryonic Survival ◽  
Nlrp3 Inflammasome Activation ◽  
Embryonic Death

Excess platelet-activation by extracellular vesicles (EVs) results in trophoblast inflammasome activation, IL-1β activation, preeclampsia (PE) and partial embryonic lethality. Furthermore, embryonic thrombomodulin (TM) deficiency, which causes embryonic lethality hallmarked by impaired trophoblast proliferation, has been linked with maternal platelet-activation. Hence, we hypothesized that placental TM loss, platelet-activation, and embryonic lethality are mechanistically linked to trophoblast inflammasome activation. Here, we uncover a unidirectional interaction of placental inflammasome activation and reduced placental TM-expression: while inflammasome inhibition did not rescue TM-null embryos from lethality, the inflammasome-dependent cytokine IL-1β reduced trophoblast TM expression and impaired pregnancy outcome. Likewise, EVs known to induce placental inflammasome activation, reduced trophoblast TM expression and proliferation. Trophoblast TM expression correlated negatively with IL-1β expression and positively with platelet numbers and trophoblast proliferation in human PE placentae, implying translational relevance. Soluble TM treatment or placental TM restoration ameliorated the EV-induced PE-like phenotype in mice, preventing placental thrombo-inflammation and embryonic death. Collectively, the lethality of TM-null embryos is not a consequence of placental NLRP3 inflammasome activation. Conversely, EV-induced placental inflammasome activation reduces placental TM expression, which promotes placental and embryonic demise. These data identify a new function of placental TM in PE and suggest that soluble TM limits thrombo-inflammatory pregnancy complications.

C3a modulates IL-1β secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation

Blood ◽  
2013 ◽  
Vol 122 (20) ◽  
pp. 3473-3481 ◽  
Author(s):  
Elham Asgari ◽  
Gaelle Le Friec ◽  
Hidekazu Yamamoto ◽  
Esperanza Perucha ◽  
Steven S. Sacks ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Human Monocytes ◽  
Nlrp3 Inflammasome Activation ◽  
Key Points ◽  
Activated Monocytes ◽  
Atp Efflux

Key Points C3aR activation increases ATP efflux, NLRP3 inflammasome activation, and IL-1β secretion in human monocytes. C3aR-activated monocytes drive Th17 responses in vitro and likely in vivo.

scholarly journals Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation

Blood ◽  
2013 ◽  
Vol 122 (20) ◽  
pp. 3405-3414 ◽  
Author(s):  
Eugenio D. Hottz ◽  
Juliana F. Lopes ◽  
Carla Freitas ◽  
Rogério Valls-de-Souza ◽  
Marcus F. Oliveira ◽  
...  
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Vascular Permeability ◽  
Nlrp3 Inflammasome ◽  
Dengue Infection ◽  
Inflammasome Activation ◽  
Dengue Virus Infection ◽  
Nlrp3 Inflammasome Activation ◽  
Key Points ◽  
Endothelium Permeability

Key Points Dengue infection triggers functional inflammasome assembly in platelets. Platelets may contribute to increased vascular permeability in dengue virus infection by synthesis and release of IL-1β.

scholarly journals Pregnane X Receptor Activation Triggers Rapid ATP Release in Primed Macrophages That Mediates NLRP3 Inflammasome Activation

2019 ◽  
Vol 370 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Grace Hudson ◽  
Kyle L. Flannigan ◽  
Vivek Krishna Pulakazhi Venu ◽  
Laurie Alston ◽  
Christina F. Sandall ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Atp Release ◽  
Pregnane X Receptor ◽  
Receptor Activation ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

scholarly journals The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype

Blood ◽  
2016 ◽  
Vol 128 (25) ◽  
pp. 2960-2975 ◽  
Author(s):  
Ashley A. Basiorka ◽  
Kathy L. McGraw ◽  
Erika A. Eksioglu ◽  
Xianghong Chen ◽  
Joseph Johnson ◽  
...  
Keyword(s):  
Cell Death ◽  
Myelodysplastic Syndrome ◽  
Nlrp3 Inflammasome ◽  
Gene Mutations ◽  
Inflammasome Activation ◽  
Biological Features ◽  
Nlrp3 Inflammasome Activation ◽  
Key Points ◽  
Founder Gene

Key Points Key biological features of MDSs are explained by NLRP3 inflammasome activation, which drives pyroptotic cell death and β-catenin activation. Alarmin signals and founder gene mutations license this redox-sensitive inflammasome platform.

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