The NLRP3 inflammasome in health and disease: the good, the bad and the ugly
P Menu,James E Vince +1 more
TLDR
Recently, inflammasome function has been implicated in more common human conditions, which raises the possibility that anti‐IL‐1 therapeutics may have broader applications than anticipated previously, and may be utilized across diverse disease states that are linked insidiously through unwanted or heightened inflammaome activity.Abstract:
While interleukin (IL)-1β plays an important role in combating the invading pathogen as part of the innate immune response, its dysregulation is responsible for a number of autoinflammatory disorders. Large IL-1β activating platforms, known as inflammasomes, can assemble in response to the detection of endogenous host and pathogen-associated danger molecules. Formation of these protein complexes results in the autocatalysis and activation of caspase-1, which processes precursor IL-1β into its secreted biologically active form. Inflammasome and IL-1β activity is required to efficiently control viral, bacterial and fungal pathogen infections. Conversely, excess IL-1β activity contributes to human disease, and its inhibition has proved therapeutically beneficial in the treatment of a spectrum of serious, yet relatively rare, heritable inflammasomopathies. Recently, inflammasome function has been implicated in more common human conditions, such as gout, type II diabetes and cancer. This raises the possibility that anti-IL-1 therapeutics may have broader applications than anticipated previously, and may be utilized across diverse disease states that are linked insidiously through unwanted or heightened inflammasome activity.read more
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Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in Major depressive disorder
Elísabet Alcocer-Gómez,Nieves Casas-Barquero,Matthew Williams,Samuel L. Romero-Guillena,Diego Cañadas-Lozano,Pedro Bullón,José Antonio Sánchez-Alcázar,José M. Navarro-Pando,Mario D. Cordero +8 more
TL;DR: The data have shown that antidepressant‐mediated autophagy may have a role in restoration of certain metabolic and immunological pathways in MDD patients, and therefore the monitoring of NLRP3 expression levels and/or IL‐1&bgr;/IL‐18 release may have clinical value in drug selection.
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NLRP3 deletion protects from hyperoxia-induced acute lung injury.
Jutaro Fukumoto,Itsuko Fukumoto,Prasanna Tamarapu Parthasarathy,Ruan Cox,Bao Huynh,Gurukumar Kollongod Ramanathan,Rajan Babu Venugopal,Diane Allen-Gipson,Richard F. Lockey,Narasaiah Kolliputi +9 more
TL;DR: This research demonstrates for the first time that NLRP3-deficient mice have suppressed inflammatory response and blunted lung epithelial cell apoptosis to HALI.
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Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages
TL;DR: It is shown for the first time that Aloe vera-mediated strong reduction of IL-1β appears to be the consequence of the reduced expression of both pro-IL-1 β as well as Nlrp3 inflammasome components via suppressing specific signal transduction pathways.
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Synovium and the Innate Inflammatory Network in Osteoarthritis Progression
TL;DR: This review focuses on the recent advancements in the understanding of innate immunity in the pathogenesis of osteoarthritis, particularly with attention to the roles of damage-associated molecular patterns, pattern recognition receptors (PPRs), and complement in synovitis development and cartilage degradation.
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The inflammasome and danger associated molecular patterns (DAMPs) are implicated in cytokine and chemokine responses following stressor exposure.
Thomas Maslanik,Lucas Mahaffey,Kate Tannura,Lida A. Beninson,Benjamin N. Greenwood,Monika Fleshner +5 more
TL;DR: The data presented establish that male F344 rats exposed to an acute severe stressor have elevated plasma concentrations of inflammatory proteins, and implicates the DAMPs uric acid and Hsp72 as important signals contributing to inflammasome-dependent inflammatory responses using a stepwise multiple regression.
References
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Journal ArticleDOI
Global cancer statistics
TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.
Journal ArticleDOI
Global cancer statistics, 2002.
TL;DR: There are striking variations in the risk of different cancers by geographic area, most of the international variation is due to exposure to known or suspected risk factors related to lifestyle or environment, and provides a clear challenge to prevention.
Journal ArticleDOI
Inflammation and cancer: back to Virchow?
TL;DR: A rationale for the use of cytokine and chemokine blockade, and further investigation of non-steroidal anti-inflammatory drugs, in the chemoprevention and treatment of malignant diseases is provided.
Journal ArticleDOI
The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
TL;DR: In this article, the inflammasome is identified as a caspase-activating complex that comprises caspases-1, casp-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs.
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Gout-associated uric acid crystals activate the NALP3 inflammasome
TL;DR: It is shown that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1β and IL-18 in mice deficient in the IL-1β receptor.