Karyopherin Alpha 2 Promotes the Inflammatory Response in Rat Pancreatic Acinar Cells Via Facilitating NF-κB Activation.
Dig Dis Sci
; 61(3): 747-57, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26526450
ABSTRACT
BACKGROUND:
Activation of the transcription factor NF-κB and expression of pro-inflammatory mediators have been considered as major events of acute pancreatitis (AP). Karyopherin alpha 2 (KPNA2), a member of the importin α family, reportedly modulates p65 subcellular localization.AIM:
This study aimed to investigate the expression and possible functions of KPNA2 in the AP cell and animal model, focusing on its association with NF-κB activation.METHODS:
An AP cell model was established with the cerulein-stimulated AR42J and isolated rat pancreatic acinar cells. The AP rat model was induced by the intraperitoneal injection of cerulein. The secretion of TNF-α, IL-6, and LDH was detected by ELISA kits and the production of NO using nitric oxide kit. Expression of KPNA2 was measured by RT-PCR and Western blot. Expression levels of IKKα, phosphorylation of p65, and total p65 were detected by Western blot. Co-localization of KPNA2 with p65 was observed by immunofluorescence assay. To determine the biological functions of KPNA2 in cerulein-induced inflammatory response, RNA interference was employed to knockdown KPNA2 expression in AR42J and isolated pancreatic acini cells.RESULTS:
Cerulein stimulated KPNA2 expression and IL-6, TNF-α, NO, and LDH production in rat pancreatic acinar cells. Cerulein triggered the phosphorylation and nuclear translocation of NF-κB p65 subunit, indicating the NF-κB activation. The co-localization and nuclear accumulation of KPNA2 and p65 were detected in cerulein-treated cells. Knocking down KPNA2 hindered cerulein-induced nuclear transportation of p65 and alleviated the subsequent inflammatory response in rat pancreatic acinar cells. Additionally, KPNA2 expression was significantly up-regulated in cerulein-induced AP rat model.CONCLUSIONS:
KPNA2-facilitated p65 nuclear translocation promotes NF-κB activation and inflammation in acute pancreatitis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pâncreas
/
Pancreatite
/
RNA Mensageiro
/
Alfa Carioferinas
/
Fator de Transcrição RelA
/
Células Acinares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Dig Dis Sci
Ano de publicação:
2016
Tipo de documento:
Article