As. Gukovskaya et al., PANCREATIC ACINAR-CELLS PRODUCE, RELEASE, AND RESPOND TO TUMOR-NECROSIS-FACTOR-ALPHA - ROLE IN REGULATING CELL-DEATH AND PANCREATITIS, The Journal of clinical investigation, 100(7), 1997, pp. 1853-1862
The aim of this study was to determine whether tumor necrosis factor-a
lpha (TNF alpha) and receptors for TNF alpha are expressed in the exoc
rine pancreas, and whether pancreatic acinar cells release and respond
to TNF alpha. Reverse transcription PCR, immunoprecipitation, and Wes
tern blot analysis demonstrated the presence of TNF alpha and 55- and
75-kD TNF alpha receptors in pancreas from control rats, rats with exp
erimental pancreatitis induced by supramaximal doses of cerulein, and
in isolated pancreatic acini. Immunohistochemistry showed TNF alpha pr
esence in pancreatic acinar cells. ELISA and bioassay measurements of
TNF alpha indicated its release from pancreatic acinar cells during in
cubation in primary culture. Acinar cells responded to TNF alpha. TNF
alpha potentiated NF-kappa B translocation into the nucleus and stimul
ated apoptosis in isolated acini while not affecting LDH release, In v
ivo studies demonstrated that neutralization of TNF alpha with an anti
body produced a mild improvement in the parameters of cerulein-induced
pancreatitis. However, TNF alpha neutralization greatly inhibited apo
ptosis in a modification of the cerulein model of pancreatitis which i
s associated with a high percentage of apoptotic cell death. The resul
ts indicate that pancreatic acinar cells produce, release, and respond
to TNF alpha. This cytokine regulates apoptosis in both isolated panc
reatic acini and experimental pancreatitis.