Diphenyleneiodonium ameliorates acute liver rejection during transplantation by inhibiting neutrophil extracellular traps formation in vivo.
Transpl Immunol
; 68: 101434, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34216758
ABSTRACT
Neutrophil extracellular traps (NETs) play critical roles in hepatic ischemic reperfusion injury (IRI) induced immune responses to inflammation. Diphenyleneiodonium (DPI) is an NADPH oxidative inhibitor that has been implicated in the regulation of NETs formation. However, the effects of NETs and their underlying mechanisms during DPI treatment of acute rejection (AR) after liver transplantation have not been elucidated. This study tested the hypothesis that blocking NETs formation by DPI treatment could be a potential therapeutic target against AR after liver transplantation. NETs were found to be excessively formed within the livers and serum of transplantation models, which could be an independent risk factor for AR. DPI was shown to alleviate hepatic injury and maintain liver functions by inhibiting NETs formation through the nicotinamide adenine dinucleotide phosphate (NADPH)/ROS/peptidylarginine deiminase 4 (PAD4) signaling pathway. NETs are highly involved in AR after liver transplantation. By inhibiting NETs formation, DPI suppresses activation of the NADPH/ROS/PAD4 signaling pathway which acts against AR after liver transplantation. Therefore, DPI is a potential candidate for the therapeutic management of AR after liver transplantation. Combination treatment containing both DPI and tacrolimus revealed a better antidamage efficacy than adjusting either treatment alone, suggesting that the joint therapy might be a promising solution in AR after liver transplantation.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Armadilhas Extracelulares
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Transpl Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
TRANSPLANTE
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China