Relationship between NF-kappaB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation.
Intra-acinar cell nuclear factor-kappaB (NF-kappaB) and trypsinogen activation are early events in secretagogue-induced acute pancreatitis. We have studied the relationship between NF-kappaB and trypsinogen activation in rat pancreas. CCK analogue caerulein induces early (within 15 min) parallel activation of both NF-kappaB and trypsinogen in pancreas in vivo as well as in pancreatic acini in vitro. However, NF-kappaB activation can be induced without trypsinogen activation by lipopolysaccharide in pancreas in vivo and by phorbol ester in pancreatic acini in vitro. Stimulation of acini with caerulein after 6 h of culture results in NF-kappaB but not trypsinogen activation. Protease inhibitors (AEBSF, TLCK, and E64d) inhibit both intracellular trypsin activity and NF-kappaB activation in caerulein stimulated acini. A chymotrypsin inhibitor (TPCK) inhibits NF-kappaB activation but not trypsin activity. The proteasome inhibitor MG-132 prevents caerulein-induced NF-kappaB activation but does not prevent trypsinogen activation. These findings indicate that although caerulein-induced NF-kappaB and trypsinogen activation are temporally closely related, they are independent events in pancreatic acinar cells. NF-kappaB activation per se is not required for the development of early acinar cell injury by supramaximal secretagogue stimulation.
Hietaranta
A J
AJ
Department of Surgery, Harvard Medical School, Boston, Massachusetts 02215, USA.
Saluja
A K
AK
Bhagat
L
L
Singh
V P
VP
Song
A M
AM
Steer
M L
ML
D000818:Animals; D002478:Cells, Cultured; D002108:Ceruletide / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism*
D007976:Leupeptins; D009097:Multienzyme Complexes; D016328:NF-kappa B; D014108:Tosylphenylalanyl Chloromethyl Ketone; D002108:Ceruletide; D014362:Trypsinogen; D004247:DNA; D014357:Trypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D013755:Tetradecanoylphorbol Acetate; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde