Relationship between NF-kappa B and trypsinogen activation in rat pancreasafter supramaximal caerulein stimulation

Intra-acinar cell nuclear factor-kappaB (NF-kappaB) and trypsinogen activat ion are early events in secretagogue-induced acute pancreatitis. We have st udied the relationship between NF-kappaB and trypsinogen activation in rat pancreas. CCK analogue caerulein induces early (within 15 min) parallel act ivation 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 wi thout trypsinogen activation by lipopolysaccharide in pancreas in vivo and by phorbol ester in pancreatic acini in vitro. Stimulation of acini with ca erulein after 6 h of culture results in NF-kappaB but not trypsinogen activ ation. Protease inhibitors (AEBSF, TLCK, and E64d) inhibit both intracellul ar trypsin activity and NF-kappaB activation in caerulein stimulated acini. A chymotrypsin inhibitor (TPCK) inhibits NF-kappaB activation but not tryp sin activity. The proteasome inhibitor MG-132 prevents caerulein-induced NF -kappaB activation but does not prevent trypsinogen activation. These findi ngs indicate that although caerulein-induced NF-kappaB and trypsinogen acti vation are temporally closely related, they are independent events in pancr eatic acinar cells. NF-kappaB activation per se is not required for the dev elopment of early acinar cell injury by supramaximal secretagogue stimulati on. (C) 2001 Academic Press.