title: Pattern of transcription factor activation in Helicobacter pylori-infected Mongolian gerbils.
abstract: OBJECTIVE
  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 IkappaB 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-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.
  
  
  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-kappaB and ISRE were late responders related to atrophy.
authors: Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Takahiko
authors: T
authors: Kudo
authors: Hong
authors: H
authors: Lu
authors: Jeng-Yih
authors: JY
authors: Wu
authors: Tomoyuki
authors: T
authors: Ohno
authors: Michael J
authors: MJ
authors: Wu
authors: Robert M
authors: RM
authors: Genta
authors: David Y
authors: DY
authors: Graham
authors: Yoshio
authors: Y
authors: Yamaoka
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori; D020672:I-kappa B Proteins / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D051720:Upstream Stimulatory Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D050684:E2F Transcription Factors; D020672:I-kappa B Proteins; D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D020928:Mitogen-Activated Protein Kinases