Abstract
Reactive oxygen species (ROS) are known to be involved in the pathogenesis of acute and chronic pancreatitis. The cholecystokinin (CCK) analog cerulein causes pathophysiological, morphological, and biochemical events similar to those observed in human acute pancreatitis. The oxidant-sensitive transcription factor NF-κB plays a critical role in the development of cerulein pancreatitis by regulating the expression of pro-inflammatory cytokines in the pancreas. Lycopene has an anti-oxidant effect in various cells. In the present study, we investigated whether cerulein induces NF-κB activation and IL-6 expression in pancreatic acinar cells and whether lycopene inhibits these events. NF-κB-DNA-binding activity was determined by electrophoretic mobility shift assay, and mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR analyses. The IL-6 concentration in the medium was determined by enzyme-linked immunosorbent assay. Our results showed that cerulein induced IL-6 expression in a time-dependent manner. NF-κB-DNA-binding activity and intracellular levels of ROS in pancreatic acinar cells were increased by cerulein. Lycopene inhibited the cerulein-induced increase in intracellular ROS, NF-κB activation, and IL-6 expression in pancreatic acinar cells in a dose-dependent manner. In conclusion, lycopene may be beneficial in the prevention and/or treatment of acute pancreatitis by inhibiting the activation of NF-κB and the expression of inflammatory cytokines through reduction in intracellular levels of ROS in pancreatic acinar cells.