Role of Histiocyte-Derived frHMGB1 as a Facilitator in Noncanonical Pyroptosis of Monocytes/Macrophages in Lethal Sepsis.
J Infect Dis
; 230(2): 298-308, 2024 Aug 16.
Article
em En
| MEDLINE
| ID: mdl-38243905
ABSTRACT
In this study, we investigated the role of the noncanonical pyroptosis pathway in the progression of lethal sepsis. Our findings emphasize the significance of noncanonical pyroptosis in monocytes/macrophages for the survival of septic mice. We observed that inhibiting pyroptosis alone significantly improved the survival rate of septic mice and that the HMGB1 A box effectively suppressed this noncanonical pyroptosis, thereby enhancing the survival of septic mice. Additionally, our cell in vitro experiments unveiled that frHMGB1, originating from lipopolysaccharide-carrying histiocytes, entered macrophages via RAGE, resulting in the direct activation of caspase 11 and the induction of noncanonical pyroptosis. Notably, A box's competitive binding with lipopolysaccharide impeded its entry into the cell cytosol. These findings reveal potential therapeutic strategies for slowing the progression of lethal sepsis by modulating the noncanonical pyroptosis pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Monócitos
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Lipopolissacarídeos
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Sepse
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Proteína HMGB1
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Piroptose
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Macrófagos
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2024
Tipo de documento:
Article