scholarly journals Prostaglandin E2Inhibits NLRP3 Inflammasome Activation through EP4 Receptor and Intracellular Cyclic AMP in Human Macrophages

2015 ◽  
Vol 194 (11) ◽  
pp. 5472-5487 ◽  
Author(s):  
Milena Sokolowska ◽  
Li-Yuan Chen ◽  
Yueqin Liu ◽  
Asuncion Martinez-Anton ◽  
Hai-Yan Qi ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Human Macrophages ◽  
Ep4 Receptor ◽  
Nlrp3 Inflammasome Activation

scholarly journals Internalization of the Membrane Attack Complex Triggers NLRP3 Inflammasome Activation and IL-1β Secretion in Human Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ines Diaz-del-Olmo ◽  
Jonathan Worboys ◽  
Fatima Martin-Sanchez ◽  
Anna Gritsenko ◽  
Ashley R. Ambrose ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Pore Formation ◽  
Membrane Attack Complex ◽  
Inflammasome Activation ◽  
Adapter Protein ◽  
Human Macrophages ◽  
Danger Signals ◽  
Nlrp3 Inflammasome Activation ◽  
Golgi Network ◽  
Stimulation Of

Interleukin 1β (IL-1β) plays a major role in inflammation and is secreted by immune cells, such as macrophages, upon recognition of danger signals. Its secretion is regulated by the inflammasome, the assembly of which results in caspase 1 activation leading to gasdermin D (GSDMD) pore formation and IL-1β release. During inflammation, danger signals also activate the complement cascade, resulting in the formation of the membrane attack complex (MAC). Here, we report that stimulation of LPS-primed human macrophages with sub-lytic levels of MAC results in activation of the NOD-like receptor 3 (NLRP3) inflammasome and GSDMD-mediated IL-1β release. The MAC is first internalized into endosomes and then colocalizes with inflammasome components; adapter protein apoptosis associated speck-like protein containing a CARD (ASC) and NLRP3. Pharmacological inhibitors established that MAC-triggered activation of the NLRP3 inflammasome was dependent on MAC endocytosis. Internalization of the MAC also caused dispersion of the trans-Golgi network. Thus, these data uncover a role for the MAC in activating the inflammasome and triggering IL-1β release in human macrophages.

scholarly journals β-Glucan–induced reprogramming of human macrophages inhibits NLRP3 inflammasome activation in cryopyrinopathies

2020 ◽  
Vol 130 (9) ◽  
pp. 4561-4573 ◽  
Author(s):  
Giorgio Camilli ◽  
Mathieu Bohm ◽  
Alícia Corbellini Piffer ◽  
Rachel Lavenir ◽  
David L. Williams ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Human Macrophages ◽  
Nlrp3 Inflammasome Activation

scholarly journals Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages

2018 ◽  
Vol 11 (1) ◽  
pp. 86-98 ◽  
Author(s):  
Angelica Montenegro Riestra ◽  
J. Andrés Valderrama ◽  
Kathryn A. Patras ◽  
Sharon D. Booth ◽  
Xing Yen Quek ◽  
...  
Keyword(s):  
Cell Death ◽  
Host Cell ◽  
Nlrp3 Inflammasome ◽  
Trichomonas Vaginalis ◽  
Inflammasome Activation ◽  
Cell Detection ◽  
Human Macrophages ◽  
Sexually Transmitted ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation

Trichomonas vaginalis is a sexually transmitted, eukaryotic parasite that causes trichomoniasis, the most common nonviral, sexually transmitted disease in the USA and worldwide. Little is known about the molecular mechanisms involved in the host immune response to this widespread parasite. Here we report that T. vaginalis induces NLRP3 inflammasome activation in human macrophages, leading to caspase-1 activation and the processing of pro-IL-1β to the mature and bioactive form of the cytokine. Using inhibitor-based approaches, we show that NLRP3 activation by T. vaginalis involves host cell detection of extracellular ATP via P2X7 receptors and potassium efflux. In addition, our data reveal that T. vaginalis inflammasome activation induces macrophage inflammatory cell death by pyroptosis, known to occur via caspase-1 cleavage of the gasdermin D protein, which assembles to form pores in the host cell membrane. We found that T. vaginalis-induced cytolysis of macrophages is attenuated in gasdermin D knockout cells. Lastly, in a murine challenge model, we detected IL-1β production in vaginal fluids in response to T. vaginalis infection in vivo. Together, our findings mechanistically dissect how T. vaginalis contributes to the production of the proinflammatory IL-1β cytokine and uncover pyroptosis as a mechanism by which the parasite can trigger host macrophage cell death.

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