| RRC ID |
67509
|
| 著者 |
Zhang T, Tsutsuki H, Islam W, Ono K, Takeda K, Akaike T, Sawa T.
|
| タイトル |
ATP exposure stimulates glutathione efflux as a necessary switch for NLRP3 inflammasome activation.
|
| ジャーナル |
Redox Biol
|
| Abstract |
The NLRP3 inflammasome is a multiprotein complex responsible for the maturation of precursor forms of interleukin (IL)-1β and IL-18 into active proinflammatory cytokines. Increasing evidence suggests that modulation of redox homeostasis contributes to the activation of the NLRP3 inflammasome. However, specific mechanistic details remain unclear. We demonstrate here that ATP exposure evoked a sharp decrease in glutathione (GSH) levels in macrophages, which led to NLRP3 inflammasome activation. We detected an increase in GSH levels in culture supernatants that was comparable to the GSH decrease in macrophages, which suggests that exposure to ATP stimulated GSH efflux. Exogenous addition of P2X7 receptor antagonist, GSH, or the oxidized form GSSG attenuated this efflux. Also, exogenous GSH or GSSG strongly inhibited NLRP3 inflammasome activation in vitro and in vivo. These data suggest that GSH efflux controls NLRP3 inflammasome activation, which may lead to development of novel therapeutic strategies for NLRP3 inflammasome-associated disorders.
|
| 巻・号 |
41
|
| ページ |
101930
|
| 公開日 |
2021-5-1
|
| DOI |
10.1016/j.redox.2021.101930
|
| PII |
S2213-2317(21)00078-1
|
| PMID |
33740502
|
| PMC |
PMC7995658
|
| MeSH |
Adenosine Triphosphate
Glutathione
Inflammasomes*
Interleukin-1beta
Macrophages
NLR Family, Pyrin Domain-Containing 3 Protein*
Reactive Oxygen Species
|
| IF |
9.986
|
| リソース情報 |
| ヒト・動物細胞 |
J774.1(RCB0434) |
