Journal ArticleDOI
Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome
Takuma Misawa,Michihiro Takahama,Tatsuya Kozaki,Hanna Lee,Jian Zou,Tatsuya Saitoh,Shizuo Akira +6 more
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TLDR
It is shown that microtubules mediated assembly of the NLRP3 inflammasome, and the creation of optimal sites for signal transduction by microtubule is required for activation of the entire NLRP2 inflammaome.Abstract:
NLRP3 forms an inflammasome with its adaptor ASC, and its excessive activation can cause inflammatory diseases. However, little is known about the mechanisms that control assembly of the inflammasome complex. Here we show that microtubules mediated assembly of the NLRP3 inflammasome. Inducers of the NLRP3 inflammasome caused aberrant mitochondrial homeostasis to diminish the concentration of the coenzyme NAD(+), which in turn inactivated the NAD(+)-dependent α-tubulin deacetylase sirtuin 2; this resulted in the accumulation of acetylated α-tubulin. Acetylated α-tubulin mediated the dynein-dependent transport of mitochondria and subsequent apposition of ASC on mitochondria to NLRP3 on the endoplasmic reticulum. Therefore, in addition to direct activation of NLRP3, the creation of optimal sites for signal transduction by microtubules is required for activation of the entire NLRP3 inflammasome.read more
Citations
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Journal ArticleDOI
Activation and regulation of the inflammasomes
TL;DR: The complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response are discussed, and the similarities to another molecular signalling platform — the apoptosome — that monitors cellular health are highlighted.
Journal ArticleDOI
Mechanisms and Functions of Inflammasomes
Mohamed Lamkanfi,Vishva M. Dixit +1 more
TL;DR: This Review summarizes recent insights into inflammasome biology and discusses the questions that remain in the field.
Journal ArticleDOI
The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation.
TL;DR: Current understanding of the mechanisms ofNLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3 are summarized.
Journal ArticleDOI
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease
Yun-Hee Youm,Kim Y. Nguyen,Ryan W. Grant,Emily L. Goldberg,Monica Bodogai,Dongin Kim,Dominic P. D’Agostino,Noah J. Planavsky,Christopher R. Lupfer,Thirumala D. Kanneganti,Seokwon Kang,Tamas L. Horvath,Tarek M. Fahmy,Peter A. Crawford,Arya Biragyn,Emad S. Alnemri,Vishwa Deep Dixit +16 more
TL;DR: In vivo, BHB or a ketogenic diet attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3-mediated diseases such as Muckle–Wells syndrome, familial cold autoinflammatory syndrome and urate crystal–induced peritonitis and the findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of theNLRP3 inflammasome.
Journal ArticleDOI
Molecular mechanisms regulating NLRP3 inflammasome activation.
TL;DR: The NLRP3 inflammasome is linked with various human autoinflammatory and autoimmune diseases and may be a promising target for anti-inflammatory therapies, according to current understanding of the mechanisms by which it is activated in the cytosol.
References
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Journal ArticleDOI
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.
Journal ArticleDOI
A role for mitochondria in NLRP3 inflammasome activation
TL;DR: It is shown that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome, and may explain the frequent association of mitochondrial damage with inflammatory diseases.
Journal ArticleDOI
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Peter Duewell,Hajime Kono,Katey J. Rayner,Katey J. Rayner,Cherilyn M. Sirois,Gregory I. Vladimer,Franz Bauernfeind,George S. Abela,Luigi Franchi,Guillermo Gabriel Nuñez,Max Schnurr,Terje Espevik,Egil Lien,Katherine A. Fitzgerald,Kenneth L. Rock,Kathryn J. Moore,Kathryn J. Moore,Samuel D. Wright,Veit Hornung,Eicke Latz,Eicke Latz +20 more
TL;DR: It is shown that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage and that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation.
Journal ArticleDOI
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization
Veit Hornung,Franz Bauernfeind,Annett Halle,Eivind O. Samstad,Eivind O. Samstad,Hajime Kono,Kenneth L. Rock,Katherine A. Fitzgerald,Eicke Latz,Eicke Latz +9 more
TL;DR: It is demonstrated that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3, which senses lysosomal damage as an endogenous 'danger' signal.
Journal ArticleDOI
Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica.
Catherine Dostert,Virginie Pétrilli,Robin van Bruggen,Chad Steele,Brooke T. Mossman,Jürg Tschopp +5 more
TL;DR: It is shown that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin-1β secretion, and support its role as a major proinflammatory “danger” receptor in particulate matter–related pulmonary diseases.
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A role for mitochondria in NLRP3 inflammasome activation
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Peter Duewell,Hajime Kono,Katey J. Rayner,Katey J. Rayner,Cherilyn M. Sirois,Gregory I. Vladimer,Franz Bauernfeind,George S. Abela,Luigi Franchi,Guillermo Gabriel Nuñez,Max Schnurr,Terje Espevik,Egil Lien,Katherine A. Fitzgerald,Kenneth L. Rock,Kathryn J. Moore,Kathryn J. Moore,Samuel D. Wright,Veit Hornung,Eicke Latz,Eicke Latz +20 more