Cholecystokinin induction ofmob-1chemokine expression in pancreatic acinar cells requires NF-κB activation

Abstract

Inflammatory mediators are involved in the early phase of acute pancreatitis, but the cellular mechanisms responsible for their generation within pancreatic cells are unknown. We examined the role of nuclear factor-κB (NF-κB) in cholecystokinin octapeptide (CCK-8)-induced mob-1 chemokine expression in pancreatic acinar cells in vitro. Supraphysiological, but not physiological, concentrations of CCK-8 increased inhibitory κB (IκB-α) degradation, NF-κB activation, and mob-1 gene expression in isolated pancreatic acinar cells. CCK-8-induced IκB-α degradation was maximal within 1 h. Expression of mob-1 was maximal within 2 h. Neither bombesin nor carbachol significantly increased mob-1 mRNA or induced IκB-α degradation. Thus the concentration, time, and secretagogue dependence of mob-1 gene expression and IκB-α degradation were similar. Inhibition of NF-κB with pharmacological agents or by adenovirus-mediated expression of the inhibitory protein IκB-α also inhibited mob-1 gene expression. These data indicate that the NF-κB signaling pathway is required for CCK-8-mediated induction of mob-1 chemokine expression in pancreatic acinar cells. This supports the hypothesis that NF-κB signaling is of central importance in the initiation of acute pancreatitis.