期刊
PANCREATOLOGY
卷 10, 期 2-3, 页码 119-128出版社
ELSEVIER SCIENCE BV
DOI: 10.1159/000290656
关键词
AR42J cell; Acinar cell; Acute pancreatitis; p38 MAP kinase; Nuclear factor-kappa B; Cholecystokinin; Tumor necrosis factor-alpha; Adenoviral vector
资金
- Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (Biomedical Laboratory Research and Development), Washington, D.C.
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Md. [R01 DK-071731]
- American Recovery and Reinvestment Act of 2009 - Supplemental Award [NIH R01 DK-071731]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK071731] Funding Source: NIH RePORTER
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-kappa B activation in exocrine pancreatic cells. Methods: AR42J cells incorporating an NF-kappa B-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-kappa B activation. Results: CCK- or TNF-alpha-stimulated NF-kappa B-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-kappa B 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-kappa B pathway activation in exocrine pancreatic cells, and thus potentially plays a role in the mechanism of acute pancreatitis pathogenesis. Copyright (C) 2010 S. Karger AG, Basel and IAP
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