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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Tomohiro Morishige,Yasuo Yoshioka,Hiroshi Inakura,Aya Tanabe,Xinglei Yao,Shogo Narimatsu,Youko Monobe,Takayoshi Imazawa,Shin-ichi Tsunoda,Yasuo Tsutsumi,Yohei Mukai,Naoki Okada,Shinsaku Nakagawa +12 more
TL;DR: It is demonstrated that unmodified microsized 1000-nm SP (mSP1000) induced higher levels of IL-1beta production than did smaller unmodified SPs and a part of NLRP3 activation pathway is revealed.
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TL;DR: The NOD-like receptors belong to the superfamily of pattern recognition receptors, a group of highly conserved molecules specialized in the recognition of invariant molecular patterns diffused across species.
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The intersection of cell death and inflammasome activation.
TL;DR: The mechanisms by which cell death signaling activates inflammasomes to initiate IL-1β-driven inflammation are reviewed, and the clinical relevance of these findings to heritable autoinflammatory diseases is highlighted.
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Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy.
Su-Mi Kim,Sang-Ho Lee,Yang Gyun Kim,Se Yun Kim,Jung-Woo Seo,Young-Wook Choi,Dong-Jin Kim,Kyung-Hwan Jeong,Tae-Won Lee,Chun-Gyoo Ihm,Kyu-Yeoun Won,Ju-Young Moon +11 more
TL;DR: Data support direct roles of hyperuricemia in activating NLRP3 inflammasomes in macrophages, promoting chemokine signaling in the proximal tubule and contributing to the progression of diabetic nephropathy through cross talk between macrophage and proximal Tubular cells.
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Comparison of non-crystalline silica nanoparticles in IL-1β release from macrophages
Wiggo J. Sandberg,Marit Låg,Jørn A. Holme,Bernd Friede,Maurizio Gualtieri,Maurizio Gualtieri,Marcin Kruszewski,Per E. Schwarze,Tonje Skuland,Magne Refsnes +9 more
TL;DR: Exposure to non-crystalline SiO2 particles in nano- and submicro-size ranges seemed to induce IL-1β release from LPS-primed RAW264.7 macrophages via similar mechanisms as crystalline silica, involving particle uptake, phagosomal leakage and activation of the NALP3 inflammasome.
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