CCK stimulates mob-1 expression and NF-kB activation via protein kinase C and intracellular Ca21

Han, Bing, and Craig D. Logsdon. CCK stimulates mob-1 expression and NF-kB activation via protein kinase C and intracellular Ca21. Am. J. Physiol. Cell Physiol. 278: C344–C351, 2000.—Supraphysiological concentrations of cholecystokinin (CCK) induce chemokine expression in rat pancreatic acini through the activation of the transcription factor NF-kB. In the current study, the intracellular signals involved in these pathophysiological effects of CCK were investigated. CCK induction of mob-1 expression in isolated rat pancreatic acini was blocked by the protein kinase C (PKC) inhibitors GF-109203X and Ro-32–0432 and by the intracellular Ca21 chelator BAPTA. CCK induced NF-kB nuclear translocation, and DNA binding was also blocked by GF109203X and BAPTA. Direct activation of PKC with TPA induced mob-1 chemokine expression and activated NF-kB DNA binding to a similar extent as did CCK. Increasing intracellular Ca21 using ionomycin had no effect on mob-1 mRNA levels or NF-kB activity. Both CCK and TPA treatments decreased inhibitory kB-a (IkB-a) levels, whereas ionomycin had no effect. However, the effects of TPA on IkB-a degradation were less complete than for CCK. In combination, TPA and ionomycin degraded IkB-a to a similar extent as CCK. Therefore, activation of NF-kB and mob-1 expression by supraphysiological CCK is likely mediated by both PKC activation and elevated intracellular Ca21.