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

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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

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Gerbillinae
Pylorus
Helicobacter pylori
Transcriptional Activation
Transcription Factors
Transcription Factor AP-1
Carrier Proteins
Phosphorylation
Gastric Mucosa
Infection
Interferons
Atrophy
Inflammation
Protein Array Analysis
Extracellular Signal-Regulated MAP Kinases
Electrophoretic Mobility Shift Assay
Mitogen-Activated Protein Kinases
Oligonucleotide Array Sequence Analysis
Stomach
Phosphotransferases

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Pattern of Transcription Factor Activation in Helicobacter pylori-Infected Mongolian Gerbils. / Kudo, Takahiko; Lu, Hong; Wu, Jeng Yih; Ohno, Tomoyuki; Wu, Michael J.; Genta, Robert M.; Graham, David Y.; Yamaoka, Yoshio.

In: Gastroenterology, Vol. 132, No. 3, 03.2007, p. 1024-1038.

Research output: Contribution to journalArticle

Kudo, T, Lu, H, Wu, JY, Ohno, T, Wu, MJ, Genta, RM, Graham, DY & Yamaoka, Y 2007, 'Pattern of Transcription Factor Activation in Helicobacter pylori-Infected Mongolian Gerbils', Gastroenterology, vol. 132, no. 3, pp. 1024-1038. https://doi.org/10.1053/j.gastro.2007.01.009
Kudo, Takahiko ; Lu, Hong ; Wu, Jeng Yih ; Ohno, Tomoyuki ; Wu, Michael J. ; Genta, Robert M. ; Graham, David Y. ; Yamaoka, Yoshio. / Pattern of Transcription Factor Activation in Helicobacter pylori-Infected Mongolian Gerbils. In: Gastroenterology. 2007 ; Vol. 132, No. 3. pp. 1024-1038.
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