Open AccessHelicobacter pylori stimulates host cyclooxygenase‐2 gene transcription: critical importance of MEK/ERK‐dependent activation of USF1/‐2 and CREB transcription factors
Author(s) -
Jüttner Stefan,
Cramer Thorsten,
Wessler Silja,
Walduck Anna,
Gao Feng,
Schmitz Frank,
Wunder Christian,
Weber Matthias,
Fischer Susan M.,
Schmidt Wolfgang E.,
Wiedenmann Bertram,
Meyer Thomas F.,
Naumann Michael,
Höcker Michael
Publication year - 2003
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1046/j.1462-5822.2003.00324.x
Subject(s) - biology , creb , helicobacter pylori , pathogenicity island , transcription (linguistics) , transcription factor , gene expression , mapk/erk pathway , gene , cancer research , virulence , microbiology and biotechnology , signal transduction , genetics , linguistics , philosophy
Summary Cyclooxygenase‐2 (COX‐2) represents the inducible key enzyme of arachidonic acid metabolism and contributes to the pathogenesis of gastroduodenal ulcers and gastric cancer. Helicobacter pylori infection is associated with elevated gastric COX‐2 levels, but the mechanisms underlying H. pylori ‐dependent cox‐2 gene expression are unclear. H. pylori stimulated cox‐2 mRNA and protein abundance in gastric epithelial cells in vitro and in vivo , and functional analysis of the cox‐2 gene promoter mapped its H. pylori ‐responsive region to a proximal CRE/Ebox element at −56 to −48. Moreover, USF1/‐2 and CREB transcription factors binding to this site were identified to transmit H. pylori ‐dependent cox‐2 transcription. Activation of MEK/ERK1/‐2 signalling by bacterial virulence factors located outside the H. pylori cag pathogenicity island ( cagPAI ) was found to mediate bacterial effects on the cox‐2 promoter. Our study provides a detailed description of the molecular pathways underlying H. pylori ‐dependent cox‐2 gene expression in gastric epithelial cells, and may thus contribute to a better understanding of mechanisms underlying H. pylori pathogenicity.