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

Academic Article

Abstract

  • 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. © 2010 Elsevier Inc.
  • Authors

    Digital Object Identifier (doi)

    Pubmed Id

  • 2979059
  • Author List

  • Williard DE; Twait E; Yuan Z; Carter AB; Samuel I
  • Start Page

  • 283
  • End Page

  • 290
  • Volume

  • 200
  • Issue

  • 2