Dominant Negative p38 Mitogen-Activated Protein Kinase Expression Inhibits NF-κB Activation in AR42J Cells

Erik Twait; Deborah E Williard; Isaac Samuel

doi:10.1159/000290656

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Dominant Negative p38 Mitogen-Activated Protein Kinase Expression Inhibits NF-κB Activation in AR42J Cells

Journal article

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Dominant Negative p38 Mitogen-Activated Protein Kinase Expression Inhibits NF-κB Activation in AR42J Cells

Erik Twait, Deborah E Williard and Isaac Samuel

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], Vol.10(2-3), pp.119-128

06/2010

DOI: 10.1159/000290656

PMCID: PMC2899148

PMID: 20453549

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Abstract

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..

p38 MAP kinase

Acute pancreatitis

Rapid Communication

Adenoviral vector

AR42J cell

Acinar cell

Cholecystokinin

Tumor necrosis factor-α

Nuclear factor-κB

Details

Title: Subtitle: Dominant Negative p38 Mitogen-Activated Protein Kinase Expression Inhibits NF-κB Activation in AR42J Cells
Creators: Erik Twait - 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
Deborah E Williard - 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
Isaac Samuel - 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
Resource Type: Journal article
Publication Details: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], Vol.10(2-3), pp.119-128
DOI: 10.1159/000290656
PMID: 20453549
PMCID: PMC2899148
NLM abbreviation: Pancreatology
ISSN: 1424-3903
eISSN: 1424-3911
Publisher: S. Karger AG
Language: English
Date published: 06/2010
Academic Unit: IIHR--Hydroscience and Engineering; Surgery
Record Identifier: 9984051509502771

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