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p8 Improves Pancreatic Response to Acute Pancreatitis by Enhancing the Expression of the Anti-inflammatory Protein Pancreatitis-associated Protein I

AuthorsVasseur, Sophie; Folch-Puy, Emma ; Hlouschek, Verena; García, Stéphane; Fiedler, Fritz; Lerch, Markus M.; Dagorn, Jean Charles; Closa, Daniel ; Iovanna, Juan Lucio
Issue Date20-Feb-2004
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Biological Chemistry 279(8=: 7199-7207 (2004)
Abstractp8 is a transcription cofactor whose expression is strongly and rapidly activated in pancreatic acinar cells during the acute phase of pancreatitis. A p8-deficient mouse strain was generated as a tool to investigate its function. Upon induction of acute pancreatitis, myeloperoxidase activity in pancreas and serum concentrations of amylase and lipase were much higher and pancreatic lesions more severe in p8-deficient mice than in wild-type, indicating that p8 expression decreased pancreatic sensitivity to pancreatitis induction. The protective mechanism might involve the pancreatitis-associated protein (PAP I), whose strong induction during pancreatitis is p8-dependent, because administration of anti-PAP I antibodies to rats increased pancreatic inflammation during pancreatitis. In addition, 100 ng/ml PAP I in the culture medium of macrophages prevented their activation by tumor necrosis factor α, strongly suggesting that PAP I was an anti-inflammatory factor. Finally, PAP I was able to inhibit NFκB activation by tumor necrosis factor α, in macrophages and in the AR42J pancreatic acinar cell line. In conclusion, p8 improves pancreatic resistance to inducers of acute pancreatitis by a mechanism implicating the expression of the anti-inflammatory protein PAP I.
Publisher version (URL)http://dx.doi.org/10.1074/jbc.M309152200
Identifiersdoi: 10.1074/jbc.M309152200
issn: 0021-9258
Appears in Collections:(IIBB) Artículos
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