Ablation of Phosphoinositide 3-Kinase-γ Reduces the Severity of Acute Pancreatitis

摘要: In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-γ (PI3Kγ) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3Kγ, we studied function of this enzyme vivo two different models acute pancreatitis. The disease was induced by supramaximal concentrations cerulein and feeding a choline-deficient/ethionine-supplemented diet. Although secretive isolated acini identical mutant control samples, both models, genetic ablation PI3Kγ significantly reduced extent acinar cell injury/necrosis. agreement with protective role apoptosis pancreatitis, PI3Kγ-deficient pancreata showed an increased number apoptotic cells, as determined terminal dUTP nick-end labeling caspase-3 activity. addition, neutrophil infiltration within tissue also reduced, suggesting dual action triggering events cells subsequent recruitment activation. Finally, lethality diet-induced pancreatitis PI3Kγ. Our results thus suggest that inhibition may be therapeutic value