Gout-associated uric acid crystals activate the NALP3 inflammasome
TLDR
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.Abstract:
Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues. Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a 'danger signal' released from dying cells, little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1beta and IL-18. Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1beta activation. Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1beta receptor (IL-1R). These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.read more
Citations
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Journal ArticleDOI
Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal-induced murine peritoneal model of acute gout.
TL;DR: It is indicated that resident macrophages, rather than infiltrating monocytes or neutrophils, are important for initiating and driving the early proinflammatory phase of acute gout.
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The role of the NLRP3 inflammasome in gout
TL;DR: This review focuses on the current understanding of the NLRP3 inflammasome and its critical role in MSU-crystal induced inflammatory gout attacks and the management of treatment-resistant acute and chronic tophaceous gout with IL-1 inhibitors.
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The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
TL;DR: It has become apparent that the cardinal feature of achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes; however, without a disease-specific biomarker, no manometric pattern is absolutely specific.
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The Nlrp3 inflammasome regulates acute graft-versus-host disease
Dragana Jankovic,Jayanthi Ganesan,Michael Bscheider,Natalie Stickel,Felix C. Weber,Greta Guarda,Marie Follo,Dietmar Pfeifer,Aubry Tardivel,Kristina Ludigs,Abdellatif Bouazzaoui,Katrin Kerl,Julius C. Fischer,Tobias Haas,Annette Schmitt-Gräff,Anand Manoharan,Leonard Müller,Jürgen Finke,Stefan F. Martin,Oliver Gorka,Christian Peschel,Jürgen Ruland,Marco Idzko,Justus Duyster,Ernst Holler,Lars E. French,Hendrik Poeck,Emmanuel Contassot,Robert Zeiser +28 more
TL;DR: Conditioning therapies before transplantation induce the release of uric acid, which triggers the NLRP3 inflammasome and IL-1β production contributing to graft-versus-host disease.
Journal ArticleDOI
Listeria monocytogenes-infected human peripheral blood mononuclear cells produce IL-1beta, depending on listeriolysin O and NLRP3.
Karolin Meixenberger,Florence Pache,Julia Eitel,Bernd Schmeck,Stefan Hippenstiel,Hortense Slevogt,Philippe Dje N'Guessan,Martin Witzenrath,Mihai G. Netea,Trinad Chakraborty,Norbert Suttorp,Bastian Opitz +11 more
TL;DR: It is demonstrated that human PBMCs produced mature IL-1β when infected with wild-type L. monocytogenes or when treated with purified LLO, and the Listeria-induced IL- 1β release was dependent on ASC, caspase-1, and NLRP3, whereas NOD2, Rip2, NLRP1,NLRP6, NL RP12, NLRC4, and AIM2 appeared to be dispensable.
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