Nuclear factor kappa B-dependent gene transcription in cholecystokinin- and tumor necrosis factor-alpha-stimulated isolated acinar cells is regulated by p38 mitogen-activated protein kinase.
BACKGROUND
Mitogen-activated protein (MAP) kinases and nuclear factor kappa B (NF-kappaB) are implicated in early stages of acute pancreatitis pathogenesis. We investigated the relationship between the p38 MAP kinase and NF-kappaB in isolated acinar cells.


METHODS
Isolated rodent acinar cells were stimulated with agonists after infection with an adenovector containing a luciferase promoter driven only by NF-kappaB and an adenovector containing the dominant negative (DN) form of p38 (empty vector in controls).


RESULTS
Initial immunoblots confirmed that the agonist stimulated p38 activation in acinar cells was substantially attenuated by DN p38 overexpression. Stimulation of native cholecystokinin (CCK)-A receptors or tumor necrosis factor-alpha (TNF-alpha) receptors promoted a significant increase in NF-kappaB-dependent gene transcription in cells infected with the empty vector, while overexpression of DN p38 significantly abrogated NF-kappaB-dependent luciferase activity.


CONCLUSIONS
These findings support our hypothesis that p38 is involved in the activation of proinflammatory nuclear transcription factors such as NF-kappaB in pancreatic exocrine cells.
Williard
Deborah E
DE
Iowa City Veterans Affairs Medical Center, Iowa City, USA.
Twait
Erik
E
Yuan
Zuobiao
Z
Carter
A Brent
AB
Samuel
Isaac
I
D000818:Animals; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D051379:Mice; D016328:NF-kappa B / Q000235:genetics*; D046790:Pancreas, Exocrine / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002766:Cholecystokinin; D048051:p38 Mitogen-Activated Protein Kinases