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. Published by Elsevier Inc.