Heat shock protein 90 inhibitors suppress pyroptosis in THP-1 cells.
Biochem J
; 477(20): 3923-3934, 2020 10 30.
Article
en En
| MEDLINE
| ID: mdl-32497199
ABSTRACT
Pyroptosis is a recently discovered inflammatory form of programmed cell death which is mostly triggered by infection with intracellular pathogens and critically contributes to inflammation. Mitigating pyroptosis may be a potential therapeutic target in inflammatory diseases. However, small chemicals to reduce pyroptosis is still elusive. In the present study, we screened 155 chemicals from a microbial natural product library and found Geldanamycin, an HSP90 inhibitor, profoundly rescued THP-1 cells from pyroptosis induced by LPS plus Nigericin treatment. Consistently, other HSP90 inhibitors, including Radicicol, 17-DMAG and 17-AAG, all ameliorated pyroptosis in THP-1 cells by suppressing the inflammasome/Caspase-1/GSDMD signal pathway in pyroptosis. HSP90 inhibition compromised the protein stability of NLRP3, a critical component of the inflammasome. Moreover, up-regulated HSP70 may also contribute to this effect. HSP90 inhibition may thus be a potential therapeutic strategy in the treatment of inflammatory diseases in which pyroptosis plays a role.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benzoquinonas
/
Proteínas HSP90 de Choque Térmico
/
Lactamas Macrocíclicas
/
Inflamasomas
/
Piroptosis
/
Inflamación
Límite:
Humans
Idioma:
En
Revista:
Biochem J
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos