Background: Mitogen-activated protein (MAP) kinases and nuclear factor kappa B (NF-κB) are implicated in early stages of acute pancreatitis pathogenesis. We investigated the relationship between the p38 MAP kinase and NF-κB 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-κB 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-α (TNF-α) receptors promoted a significant increase in NF-κB-dependent gene transcription in cells infected with the empty vector, while overexpression of DN p38 significantly abrogated NF-κB-dependent luciferase activity. Conclusions: These findings support our hypothesis that p38 is involved in the activation of proinflammatory nuclear transcription factors such as NF-κB in pancreatic exocrine cells.
Bibliographical noteFunding Information:
This material is based upon work supported in part by a VA Merit Review Award (to I.S.), the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (Biomedical Laboratory Research and Development) , Washington DC; Grant DK-071731 (to I.S.), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health , Bethesda, MD; and NIH grants ES-015981 and ES-014871 (to A.B.C.), National Institutes of Health, Bethesda, MD.
- Acinar cell
- Acute pancreatitis
- Adenoviral vector
- MAP kinase