Lower Temperatures Exacerbate NLRP3 Inflammasome Activation by Promoting Monosodium Urate Crystallization, Causing Gout.
Cells
; 10(8)2021 07 29.
Article
en En
| MEDLINE
| ID: mdl-34440688
ABSTRACT
Gout is a recurrent and chronic form of arthritis caused by the deposition of monosodium urate (MSU) crystals in the joints. Macrophages intake MSU crystals, the trigger for NLRP3 inflammasome activation, which leads to the release of interleukin (IL)-1ß and results in the flaring of gout. The effects of temperature, an environmental factor for MSU crystallization, on IL-1ß secretion have not been well studied. This study examined the effects of temperature on inflammasome activation. Specific triggers activated canonical inflammasomes (NLRP3, NLRC4, and AIM2) in murine macrophages at various temperatures (25, 33, 37, 39, and 42 °C). The maturation of IL-1ß and caspase-1 was measured as an indicator for inflammasome activation. As expected, the optimal temperature of inflammasome activation was 37 °C. The MSU crystal-mediated activation of inflammasome increased at temperatures lower than 37 °C and decreased at higher temperatures. MSU crystals at lower temperatures enhanced IL-1ß secretion via the NLRP3 inflammasome pathway. A lower temperature promoted the formation of MSU crystals without changing phagocytosis. Overall, lower temperatures form more MSU crystals and enhance NLRP3 inflammasome activation. In light of these findings, it is possible that hyperthermia therapy may reduce gout flaring.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Temperatura
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Ácido Úrico
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Inflamasomas
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Proteína con Dominio Pirina 3 de la Familia NLR
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Gota
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Macrófagos
Límite:
Animals
Idioma:
En
Revista:
Cells
Año:
2021
Tipo del documento:
Article