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

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 a member of the importin α family, reportedly modulates p65 subcellular localization. AIM:This study aimed to investigate the expression and possible functions of 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 Kduanyu15352 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 Kduanyu15352 with p65 was observed by immunofluorescence assay. To determine the biological functions of Kduanyu15352 in cerulein-induced inflammatory response, RNA interference was employed to knockdown Kduanyu15352 expression in AR42J and isolated pancreatic acini cells. RESULTS:Cerulein stimulated Kduanyu15352 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 Kduanyu15352 and p65 were detected in cerulein-treated cells. Knocking down Kduanyu15352 hindered cerulein-induced nuclear transportation of p65 and alleviated the subsequent inflammatory response in rat pancreatic acinar cells. Additionally, Kduanyu15352 expression was significantly up-regulated in cerulein-induced AP rat p65 nuclear translocation promotes NF-κB activation and inflammation in acute pancreatitis.

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