Relationship between NF-κB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation

Antti J. Hietaranta, Ashok K. Saluja, Lakshmi Bhagat, Vijay P. Singh, Albert M. Song, Michael L. Steer

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Intra-acinar cell nuclear factor-κB (NF-κB) and trypsinogen activation are early events in secretagogue-induced acute pancreatitis. We have studied the relationship between NF-κB and trypsinogen activation in rat pancreas. CCK analogue caerulein induces early (within 15 rain) parallel activation of both NF-κB and trypsinogen in pancreas in viva as well as in pancreatic acini in vitro. However, NF-κB activation can be induced without trypsinogen activation by lipopolysaccharide in pancreas in viva and by phorbol ester in pancreatic acini in vitro. Stimulation of acini with caerulein after 6 h of culture results in NF-κB but not trypsinogen activation. Protease inhibitors (AEBSF, TLCK, and E64d) inhibit both intracellular trypsin activity and NF-κB activation in caerulein stimulated acini. A chymotrypsin inhibitor (TPCK) inhibits NF-κB activation but not trypsin activity. The proteasome inhibitor MG-132 prevents caerulein-induced NF-κB activation but does not prevent trypsinogen activation. These findings indicate that although caerulein-induced NF-κB and trypsinogen activation are temporally closely related, they are independent events in pancreatic acinar cells. NF-κB activation per se is not required for the development of early acinar cell injury by supramaximal secretagogue stimulation.

Original languageEnglish (US)
Pages (from-to)388-395
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume280
Issue number1
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
These studies were supported by NIH Grant DK-31396. Antti Hietaranta was financially supported by Finnish Academy of Sciences, Sigrid Jusélius Foundation, Finnish Cultural Foundation, Maud Kuistila Foundation, and Finnish Foundation for Alcohol Studies.

Keywords

  • Acinar cell injury
  • Caerulein
  • Digestive enzymes
  • Nuclear factor-κB
  • Pancreas
  • Transcription factor

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