Pattern of Transcription Factor Activation in Helicobacter pylori-Infected Mongolian Gerbils

Takahiko Kudo, Hong Lu, Jeng Yih Wu, Tomoyuki Ohno, Michael J. Wu, Robert M. Genta, David Y. Graham, Yoshio Yamaoka

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Background & Aims: Helicobacter pylori interact with epithelial cells resulting in activation of cellular signaling pathways leading to an inflammatory response. The pattern and timing of transcription factor activation in H pylori-infected gastric mucosa remain unclear. We investigated the roles of transcription factors in the gastric mucosa of H pylori-infected gerbils over the course of the infection. Methods: Six-week-old male Mongolian gerbils were inoculated orally with H pylori TN2GF4 or isogenic cagE mutants and examined at 1, 3, 9, and 18 months. We examined the expression of 54 transcription factors using DNA/protein arrays and electrophoretic mobility shift assays. Phosphorylation status of mitogen-activated protein kinases and IκB were evaluated by immunoblot and immunohistochemistry. Results: Ten transcription factors were up-regulated by H pylori infection. Six of these factors, including activator protein-1 (AP-1) and cAMP responsive element binding protein (CREB), reached maximal levels at 3 months and were strongly correlated with cellular inflammation and ulceration. Phosphorylation of extracellular signal-regulated kinase correlated with activation of AP-1 and CREB. Levels of nuclear factor-κB and interferon-stimulated responsive element (ISRE) peaked at 18 months and correlated with the presence of severe atrophy and with phosphorylation of Jun-N-terminal kinase (JNK), p38, and IκB. Conclusions: The gastric mucosal transcription factors induced by H pylori infection differed according to the phase and outcome of infection; AP-1 and CREB levels were early responders related to inflammation and ulceration, whereas NF-κB and ISRE were late responders related to atrophy.

Original languageEnglish (US)
Pages (from-to)1024-1038
Number of pages15
JournalGastroenterology
Volume132
Issue number3
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Kudo, T., Lu, H., Wu, J. Y., Ohno, T., Wu, M. J., Genta, R. M., Graham, D. Y., & Yamaoka, Y. (2007). Pattern of Transcription Factor Activation in Helicobacter pylori-Infected Mongolian Gerbils. Gastroenterology, 132(3), 1024-1038. https://doi.org/10.1053/j.gastro.2007.01.009