NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals

Duewell, Peter; Kono, Hajime; Rayner, Katey J.; Sirois, Cherilyn M.; Vladimer, Gregory I.; Bauernfeind, Franz; Abela, George S.; Franchi, Luigi; Nuñez, Guillermo Gabriel; Schnurr, Max; Espevik, Terje; Lien, Egil; Fitzgerald, Katherine A.; Rock, Kenneth L.; Moore, Kathryn J.; Wright, Samuel D.; Hornung, Veit; Latz, Eicke

doi:10.1038/nature08938

Cited by 3,275 publications

(3,064 citation statements)

References 28 publications

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“…The formation of cholesterol crystals, which is easily observed in the lipid-rich necrotic core and often referred to as "the gruel," is indicative of disruption in cholesterol metabolism during the development of atherosclerosis. Moreover, the cholesterol crystals in macrophages promote the maturation and secretion of interleukin-1β (IL-1β) and IL-18 (Duewell et al, 2010).…”

Section: Re-esterification Of Free Cholesterolmentioning

confidence: 99%

Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis

2012

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Section: Re-esterification Of Free Cholesterolmentioning

confidence: 99%

Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis

2012

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“…Pyroptosis is a proinflammatory response that is triggered by a variety of pathologic stimuli, including myocardial infarction, stroke, and malignancy. Various studies have indicated that pyroptosis is intrinsically involved in the development of infectious diseases, nervous system disorders, and atherosclerotic processes 17, 18, 19. Pyroptosis is thought to be a key modulator of the immune response to microbial infection, while pathogens that have evolved and developed mechanisms to bypass pyroptosis demonstrate enhanced disease‐causing and septic potential 20…”

Section: Introductionmentioning

confidence: 99%

VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia–reperfusion injury in rats

Zhao

Huang

Alam

et al. 2018

American Journal of Transplantation

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Clinical evidence has indicated a possible link between renal injury and remote liver injury. We investigated whether extracellular histone mediates remote hepatic damage after renal graft ischemia–reperfusion injury, while vascular endothelial growth factor (VEGF) is protective against remote hepatic injury. In vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown‐Norway renal graft was stored in 4°C preservation solution for 24 hours and then transplanted into a Lewis rat recipient; blood samples and livers from recipients were harvested 24 hours after surgery. Prolonged cold ischemia in renal grafts enhanced liver injury 24 hours after engraftment. Caspase‐1, ASC, NLRP3, and AIM2 expressions in hepatocyte, CD68+‐infiltrating macrophages, tissue, and serum interleukin‐1β and ‐18 were greatly elevated, indicating that pyroptosis occurred in the liver and resulted in acute liver functional impairment. Blocking the caspase‐1 pathway decreased the number of necrotic hepatocytes. VEGF treatment suppressed the hepatocyte pyroptosis and liver function was partially restored. Our data suggested that renal allograft ischemia–reperfusion injury is likely associated with acute liver damage due to hepatocyte pyroptosis induced by histone and such injury may be protected by VEGF administration. VEGF, therefore, may serve as a new strategy against other remote organ injuries related to renal transplantation.

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“…À l'heure actuelle, sept NLR ont été identifiés comme inducteurs d'une activité inflammasome. NLRP3 (ou cryopyrine), le plus largement étudié, est impliqué dans la détection de nombreux signaux de danger, et des anomalies intrinsèques de ce récepteur sont la cause de diverses maladies affectant l'homme [6][7][8]. NLRP1, NLRP7 et les complexes NLRB/NLRC4 ont un rôle plus spécialisé dans la détection de PAMP.…”

Section: Description Des Inflammasomesunclassified

“…• Une autre voie d'activation de NLRP3 a été proposée dans le cas des particules, telles que l'amiante ou la silice [7,19], ou des cristaux d'acide urique [8] (responsables des crises de goutte), de cholestérol [6] ou d'hémozoïne (un cristal dérivé de l'hémoglobine qui se forme lors des infections à Plasmodium falciparum, un agent du paludisme [54] (➜), ou enfin de la protéine -amyloïde (maladie d'Alzheimer) [20]. Ces cristaux et particules peuvent entraîner une rupture des lysosomes ou des phagolysosomes associée à un relargage du contenu de ces organites dans le cytosol.…”

Section: L'activation De Nlrp3unclassified

Les inflammasomes

Jamilloux

Henry

2013

Med Sci (Paris)

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NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals

Cited by 3,275 publications

References 28 publications

Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis

Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis

VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia–reperfusion injury in rats

Les inflammasomes

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