Nuclear factor kappa B-dependent gene transcription in cholecystokinin- and tumor necrosis factor-α-stimulated isolated acinar cells is regulated by p38 mitogen-activated protein kinase

BACKGROUND: Mitogen-activated protein (MAP) kinases and nuclear factor kappa B (NF-kappa B) are implicated in early stages of acute pancreatitis pathogenesis. We investigated the relationship between the p38 MAP kinase and NF-kappa B 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-kappa B 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-kappa B-dependent gene transcription in cells infected with the empty vector, while overexpression of DN p38 significantly abrogated NF-kappa B-dependent luciferase activity. CONCLUSIONS: These findings support our hypothesis that p38 is involved in the activation of proinflammatory nuclear transcription factors such as NF-kappa B in pancreatic exocrine cells. Published by Elsevier Inc.