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Karyopherin Alpha 2 Promotes the Inflammatory Response in Rat Pancreatic Acinar Cells Via Facilitating NF-κB Activation.

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.

journal_name

Dig Dis Sci

journal_title

Digestive diseases and sciences

authors

Cai Y,Shen Y,Gao L,Chen M,Xiao M,Huang Z,Zhang D

doi

10.1007/s10620-015-3948-6

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

747-57

issue

eissn

0163-2116

issn

1573-2568

pii

10.1007/s10620-015-3948-6

journal_volume

pub_type

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Karyopherin Alpha 2 Promotes the Inflammatory Response in Rat Pancreatic Acinar Cells Via Facilitating NF-κB Activation.