CARD9 gene silencing with siRNA protects rats against severe acute pancreatitis: CARD9-dependent NF-κB and P38MAPKs pathway.
J Cell Mol Med
; 21(6): 1085-1093, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-27957800
ABSTRACT
We previously reported the up-regulation of caspase recruitment domain 9 (CARD9) expressions in severe acute pancreatitis (SAP) patients, but little is known about its regulation. In this study, small interfering RNA (siRNA) was used to reduce the levels of CARD9 expression in sodium taurocholate-stimulated SAP rats. CARD9 was overexpressed in SAP rats, which correlated with the severity of pancreatitis. When compared to the untreated group, the cohort that received the siRNA treatment demonstrated a significant reduction in pancreatic injury, neutrophil infiltration, myeloperoxidase activity and pro-inflammatory cytokines. Furthermore, siRNAs showed that the reduction of CARD9 in SAP rats down-regulated the expression of NF-κBp65 and P38MAPK which are involved in the transcription and release of a wide variety of inflammatory cytokines. These findings provide evidence that CARD9 is up-regulated in SAP rats and acts as a potential therapeutic target for the treatment thereof. Blocking the activation of NF-κB and P38MAPK via siRNA-mediated gene knock-down of CARD9 appears to reduce the inflammatory response in pancreatic tissue.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pancreatite
/
Proteínas Quinases p38 Ativadas por Mitógeno
/
Fator de Transcrição RelA
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Proteínas Adaptadoras de Sinalização CARD
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China