담도 , 췌장 : Cerulein 에 의해 과자극된 백서 선방세포내 Trypsinogen 의 활성화에서 NF - kB 와 PI3 - K 의 역할 = Biliary Tract and Pancreas : The Role of Nuclear Factor kB and Phosphatidylinositol 3 - kinase in Trypsinogen Activation in Cerulein - Stimulated Rat Pancreatic Acini

다국어 초록 (Multilingual Abstract)

Background/Aims: Intra-acinar cell activation of trypsinogen is a critical event in cerulein-induced pancreatitis. However, little is known about the intracellular signal transduction systems involved in trypsinogen activation. This study focused on the role of NF-kB and PI3-K involved in intracellular signal transduction systems to activate trypsinogen. Methods: Pancreatic acinar cells were prepared from male Wistar rats and nuclear factor kB (NF-kB) inhibitor, pyrolidine dithiocarbamate and N-acetylcysteine, or phosphatidylinositol 3-kinase (PI3-K) inhibitor, wortmannin and LY294002 were applied to each of a series of acinar cell cultures. Then, a supraphysiological (100 nM) concentration of cerulein was applied to the pretreated cells and the untreated control cells. Trypsinogen activation was detected by measuring trypsin activity from acinar cell homogenates and expressed as % of cerulein stimulated cells. The level of NF-kB activity was checked for the nuclear extracts, using electrophoretic mobility shift assay. Results: NF-kB activation in the acinar cells after cerulein hyperstimulation displayed a biphasic process over time. Both NF-kB inhibitors partially suppressed trypsinogen activation while the PI3-K inhibitors inhibited trypsinogen activation almost completely. NF-kB activity was blocked by pyrolidine dithiocarbamate or N-acetylcysteine but not by wortmannin or LY294002. Conclusions: Trypsinogen is activated in cerulein hyperstimulated acinar cells by PI3-K or NF-kB pathway, independently. (Korean J Gastroenterol 2001;38：427-432)