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Nat Commun ; 9(1): 2223, 2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29884801

RESUMO

Macrophage migration inhibitory factor (MIF) exerts multiple effects on immune cells, as well as having functions outside the immune system. MIF can promote inflammation through the induction of other cytokines, including TNF, IL-6, and IL-1 family cytokines. Here, we show that inhibition of MIF regulates the release of IL-1α, IL-1ß, and IL-18, not by affecting transcription or translation of these cytokines, but via activation of the NLRP3 inflammasome. MIF is required for the interaction between NLRP3 and the intermediate filament protein vimentin, which is critical for NLRP3 activation. Further, we demonstrate that MIF interacts with NLRP3, indicating a role for MIF in inflammasome activation independent of its role as a cytokine. These data advance our understanding of how MIF regulates inflammation and identify it as a factor critical for NLRP3 inflammasome activation.


Assuntos
Inflamassomos/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Proteínas de Filamentos Intermediários/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ligação Proteica , Células THP-1
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