Pancreatic acinar cells produce, release, and respond to tumor necrosis factor-α. Role in regulating cell death and pancreatitis

Abstract

The aim of this study was to determine whether tumor necrosis factor-α (TNFα) and receptors for TNFα are expressed in the exocrine pancreas, and whether pancreatic acinar cells release and respond to TNFα. Reverse transcription PCR, immunoprecipitation, and Western blot analysis demonstrated the presence of TNFα and 55- and 75-kD TNFα receptors in pancreas from control rats, rats with experimental pancreatitis induced by supramaximal doses of cerulein, and in isolated pancreatic acini. Immunohistochemistry showed TNFα presence in pancreatic acinar cells. ELISA and bioassay measurements of TNFα indicated its release from pancreatic acinar cells during incubation in primary culture. Acinar cells responded to TNFα. TNFα potentiated NF-κB translocation into the nucleus and stimulated apoptosis in isolated acini while not affecting LDH release. In vivo studies demonstrated that neutralization of TNFα with an antibody produced a mild improvement in the parameters of cerulein-induced pancreatitis. However, TNFα neutralization greatly inhibited apoptosis in a modification of the cerulein model of pancreatitis which is associated with a high percentage of apoptotic cell death. The results indicate that pancreatic acinar cells produce, release, and respond to TNFα. This cytokine regulates apoptosis in both isolated pancreatic acini and experimental pancreatitis.