Low pH and Helicobacter pylori increase nuclear factor kappa B binding in gastric epithelial cells: A common pathway for epithelial cell injury?
✍ Scribed by Dermot O'Toole; Mohamed M.M. Abdel-Latif; Aideen Long; Henry J. Windle; Anne M. Murphy; Andrew Bowie; Luke A.J. O'Neill; Donald G. Weir; Dermot Kelleher
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 238 KB
- Volume
- 96
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Helicobacter pylori infection results in peptic ulceration and chronic gastritis through mechanisms which are not fully elucidated. Live H. pylori activate the pro‐inflammatory transcription factor NF‐κB in gastric epithelial cells. Patients may have peptic ulcer disease in the absence of H. pylori infection; therefore other factors contribute to the inflammatory process. Maximal acid output in patients with H. pylori infection and duodenal ulceration is significantly increased indicating a role for acid in the pathogenesis of mucosal ulceration. The effect of low pH on NF‐κB activation in gastric epithelial cells has not been studied. Human gastric epithelial cells (AGS) were exposed to a range of pH changes in the presence or absence of H. pylori. NF‐κB DNA‐binding and cytosolic IκB‐α were measured using electrophoretic mobility shift assay and Western blotting. NF‐κB DNA‐binding in gastric epithelial cells dramatically increased when the pH of the culture medium decreased. Increases in NF‐κB nuclear binding were paralleled by decreasing amounts of cytosolic IκB‐α. These findings were similar but less potent than those observed when cells were exposed to H. pylori. Low pH resulted in enhancement of H. pylori‐induced NF‐κB nuclear binding. DNA binding of NF‐κB activation secondary to low pH was attenuated by PD98059 but not by SB203580. Similar to H. pylori, low pH potently and independently augments NF‐κB nuclear binding in AGS cells and such activation appears to be mediated through MEK1‐dependant signaling pathways. © 2005 Wiley‐Liss, Inc.