CCK independently activates intracellular trypsinogen and NF-κB in rat pancreatic acinar cells

Bing Han, J. I. Baoan, Craig D. Logsdon

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

In the cholecystokinin (CCK) hyper-stimulation model of acute pancreatitis, two early intracellular events, activation of trypsinogen and activation of nuclear factor-κB (NF-κB), are thought to be important in the development of the disease. In this study, the relationship between these two events was investigated. NF-κB activity was monitored by using a DNA binding assay and mob·1 chemokine gene expression. Intracellular trypsin activity was measured by using a fluorogenic substrate. Protease inhibitors including FUT-175, Pefabloc, and E-64d prevented CCK stimulation of intracellular trypsinogen and NF-κB activation. Likewise, the NF-κB inhibitors pyrrolidine dithiocarbamate and N-acetyl-L-cysteine inhibited CCK stimulation of NF-κB and intracellular trypsinogen activation. These results suggested a possible codependency of these two events. However, CCK stimulated NF-κB activation in Chinese hamster ovary-CCKA cells, which do not express trypsinogen, indicating that trypsin is not necessary for CCK activation of NF-κB. Furthermore, adenovirus-mediated expression in acinar cells of active p65 subunits to stimulate NF-κB, or of inhibitory κB-α molecules to inhibit NF-κB, did not affect either basal or CCK-mediated trypsinogen activation. Thus trypsinogen and NF-κB activation are independent events stimulated by CCK.

Original languageEnglish (US)
Pages (from-to)C465-C472
JournalAmerican Journal of Physiology - Cell Physiology
Volume280
Issue number3 49-3
DOIs
StatePublished - 2001

Keywords

  • Cholecystokinin
  • Inflammation
  • Nuclear factor-κB
  • Pancreatitis

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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