Dominant negative p38 mitogen-activated protein kinase expression inhibits NF-kappaB activation in AR42J cells.

Pancreatology

Surgical Services, Iowa City Veterans Affairs Medical Center, and Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.

Published: September 2010

Background: The role of the p38 mitogen-activated protein (MAP) kinase in acute pancreatitis pathogenesis is controversial. We hypothesize that p38 plays a role in regulating NF-kappaB activation in exocrine pancreatic cells.

Methods: AR42J cells incorporating an NF-kappaB-responsive luciferase reporter, with and without adenoviral transduction of DNp38, were stimulated with cholecystokinin (CCK) or tumor necrosis factor-alpha (TNF-alpha) prior to measuring NF-kappaB activation.

Results: CCK- or TNF-alpha-stimulated NF-kappaB-dependent gene transcription (luciferase assay) was substantially subdued by DNp38 expression. These findings were confirmed by electrophoretic mobility shift assay. Nuclear translocation of the p65 NF-kappaB subunit following agonist stimulation was evident (supershift). Characterization studies showed excellent adenoviral infection efficiency and cell viability in our AR42J cell model. Agonist-stimulated dose- and time-dependent p38 activation, with inhibition by DNp38 expression, was also confirmed.

Conclusion: The p38 MAP kinase regulates NF-kappaB pathway activation in exocrine pancreatic cells, and thus potentially plays a role in the mechanism of acute pancreatitis pathogenesis..

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2899148PMC
http://dx.doi.org/10.1159/000290656DOI Listing

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