The NLRP3 inflammasome in health and disease: the good, the bad and the ugly
P Menu,James E Vince +1 more
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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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Ambiguities in NLRP3 inflammasome regulation: is there a role for mitochondria?
TL;DR: Although many mechanisms have been proposed for activating NLRP3, no unified model has yet to gain acceptance and further research is required to clarify how the mitochondria might influenceNLRP3 activity.
Journal ArticleDOI
The Role of the Immune Response in Age-Related Macular Degeneration
Scott M. Whitcup,Akrit Sodhi,John P. Atkinson,V. Michael Holers,Debasish Sinha,Bärbel Rohrer,Andrew D. Dick,Andrew D. Dick +7 more
TL;DR: This review summarizes discussions from the fifth annual conference of the Arnold and Mabel Beckman Initiative for Macular Research by the Inflammation and Immune Response Task Force on the role of inflammatory immune responses, including complement, inflammasomes, adaptiveimmune responses, and para-inflammation.
Journal ArticleDOI
A novel "complement-metabolism-inflammasome axis" as a key regulator of immune cell effector function
TL;DR: This review summarizes recent advances in knowledge about complement‐mediated inflammasome activation, with a specific focus on a novel “complement – metabolism – NLRP3 inflammaome axis.”
Journal ArticleDOI
NLRP3 Inflammasome and MS/EAE.
Makoto Inoue,Mari L. Shinohara +1 more
TL;DR: The NLRP3 inflammasome in MS and EAE development is discussed and it is shown that the NLRP2 inflammaome exacerbates experimental autoimmune encephalomyelitis (EAE), an animal model of MS, although EAE can also develop without the NL RP3 infammasome.
Journal ArticleDOI
Radiation Exposure Induces Inflammasome Pathway Activation in Immune Cells
Veit M. Stoecklein,Akinori Osuka,Shizu Ishikawa,Madeline R. Lederer,Lorenz Wanke-Jellinek,James A. Lederer +5 more
TL;DR: It is shown that radiation induces a dose-dependent increase in inflammasome activation in macrophages, dendritic cells, NK cells, T cells, and B cells as judged by cleaved caspase-1 detection in cells and that allopurinol prevented radiation-induced inflammaome activation.
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