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Pattern of transcription factor activation in Helicobacter pylori-infected Mongolian gerbils.


ABSTRACT: 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.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 IkappaB were evaluated by immunoblot and immunohistochemistry.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-kappaB 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 IkappaB.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-kappaB and ISRE were late responders related to atrophy.

SUBMITTER: Kudo T 

PROVIDER: S-EPMC3131413 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Pattern of transcription factor activation in Helicobacter pylori-infected Mongolian gerbils.

Kudo Takahiko T   Lu Hong H   Wu Jeng-Yih JY   Ohno Tomoyuki T   Wu Michael J MJ   Genta Robert M RM   Graham David Y DY   Yamaoka Yoshio Y  

Gastroenterology 20070105 3


<h4>Background and aims</h4>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.<h4>Methods</h4>Six-week-old male Mongolian gerbils were inoculated orally with H py  ...[more]

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