Journal ArticleDOI
The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.
Alberto Baroja-Mazo,Fátima Martín-Sánchez,Ana I. Gomez,Carlos Martinez,Joaquín Amores-Iniesta,Vincent Compan,Maria Barberà-Cremades,Jordi Yagüe,Estibaliz Ruiz-Ortiz,Jordi Anton,Segundo Buján,Isabelle Couillin,David Brough,Juan I. Aróstegui,Pablo Pelegrín +14 more
Reads0
Chats0
TLDR
These findings support a model whereby the NLRP3 inflammasome, acting as an extracellular oligomeric complex, amplifies the inflammatory response.Abstract:
Assembly of the NLRP3 inflammasome activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1β and thereby serves a central role in the inflammatory response and in diverse human diseases. Here we found that upon activation of caspase-1, oligomeric NLRP3 inflammasome particles were released from macrophages. Recombinant oligomeric protein particles composed of the adaptor ASC or the p.D303N mutant form of NLRP3 associated with cryopyrin-associated periodic syndromes (CAPS) stimulated further activation of caspase-1 extracellularly, as well as intracellularly after phagocytosis by surrounding macrophages. We found oligomeric ASC particles in the serum of patients with active CAPS but not in that of patients with other inherited autoinflammatory diseases. Our findings support a model whereby the NLRP3 inflammasome, acting as an extracellular oligomeric complex, amplifies the inflammatory response.read more
Citations
More filters
Journal ArticleDOI
Inflammasomes: mechanism of assembly, regulation and signalling
Petr Broz,Vishva M. Dixit +1 more
TL;DR: This Review discusses the recent developments in inflammasome research with a focus on the molecular mechanisms that govern inflammaome assembly, signalling and regulation.
Journal ArticleDOI
Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases.
TL;DR: The central role of inflammatory caspases and pyroptosis in mediating immunity to infection and clearance of pathogens is described.
Journal Article
Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria (111.33)
Edward A. Miao,Irina A. Leaf,Piper M. Treuting,Dat P. Mao,Anasuya Sarkar,Mark D. Wewers,Alan Aderem +6 more
TL;DR: It is demonstrated that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.
Journal ArticleDOI
Keeping It All Going—Complement Meets Metabolism
Martin Kolev,Claudia Kemper +1 more
TL;DR: Current knowledge about complement’s emerging relationship with the cellular metabolism machinery is covered with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions.
Journal ArticleDOI
NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria
Zhenyu Zhong,Atsushi Umemura,Atsushi Umemura,Elsa Sanchez-Lopez,Shuang Liang,Shabnam Shalapour,Jerry Wong,Feng He,Daniela Boassa,Guy Perkins,Syed Raza Ali,Matthew D. McGeough,Mark H. Ellisman,Ekihiro Seki,Ekihiro Seki,Åsa B. Gustafsson,Hal M. Hoffman,Maria T. Diaz-Meco,Jorge Moscat,Michael Karin +19 more
TL;DR: The "NF-κB-p62-mitophagy" pathway is a macrophage-intrinsic regulatory loop through which NF-κBs restrains its own inflammation-promoting activity and orchestrates a self-limiting host response that maintains homeostasis and favors tissue repair.
References
More filters
Journal ArticleDOI
Neutrophil extracellular traps kill bacteria
Volker Brinkmann,Ulrike Reichard,Christian Goosmann,Beatrix Fauler,Yvonne Uhlemann,David S. Weiss,Yvette Weinrauch,Yvette Weinrauch,Arturo Zychlinsky +8 more
TL;DR: It is described that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria, which degrade virulence factors and kill bacteria.
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
Immunological and Inflammatory Functions of the Interleukin-1 Family
TL;DR: The IL-1 family includes members that suppress inflammation, both specifically within the IL-2 family but also nonspecifically for TLR ligands and the innate immune response.
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
Cryopyrin activates the inflammasome in response to toxins and ATP
Sanjeev Mariathasan,David S. Weiss,Kim Newton,Jacqueline McBride,Karen O'Rourke,Meron Roose-Girma,Wyne P. Lee,Yvette Weinrauch,Denise M. Monack,Vishva M. Dixit +9 more
TL;DR: It is shown that cryopyrin-deficient macrophages cannot activate caspase-1 in response to Toll-like receptor agonists plus ATP, the latter activating the P2X7 receptor to decrease intracellular K+ levels.