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

BACKGROUND AND 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 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.

[1]  G. Leontiadis,et al.  Helicobacter pylori infection. , 2009, BMJ clinical evidence.

[2]  Y. Yamaji,et al.  CagA protein secreted by the intact type IV secretion system leads to gastric epithelial inflammation in the Mongolian gerbil model , 2006, The Journal of pathology.

[3]  Y. Ben-Neriah,et al.  NF-κB inhibition: A double-edged sword in cancer? , 2006 .

[4]  D. Graham,et al.  Regulation of RANTES Promoter Activation in Gastric Epithelial Cells Infected with Helicobacter pylori , 2005, Infection and Immunity.

[5]  D. Graham,et al.  Regulation of interleukin-6 promoter activation in gastric epithelial cells infected with Helicobacter pylori. , 2005, Molecular biology of the cell.

[6]  Michael Karin,et al.  NF-κB: linking inflammation and immunity to cancer development and progression , 2005, Nature Reviews Immunology.

[7]  I. Verma,et al.  Inflammation-associated cancer: NF-κB is the lynchpin , 2005 .

[8]  G. Rieder,et al.  Helicobacter pylori cag-type IV secretion system facilitates corpus colonization to induce precancerous conditions in Mongolian gerbils. , 2005, Gastroenterology.

[9]  D. Graham,et al.  Roles of virD4 and cagG genes in the cag pathogenicity island of Helicobacter pylori using a Mongolian gerbil model , 2005, Gut.

[10]  D. Graham,et al.  Natural History of Gastric Mucosal Cytokine Expression in Helicobacter pylori Gastritis in Mongolian Gerbils , 2005, Infection and Immunity.

[11]  J. Koistinaho,et al.  Pyrrolidine dithiocarbamate inhibits translocation of nuclear factor kappa‐B in neurons and protects against brain ischaemia with a wide therapeutic time window , 2004, Journal of neurochemistry.

[12]  D. Graham,et al.  Role of interferon-stimulated responsive element-like element in interleukin-8 promoter in Helicobacter pylori infection. , 2004, Gastroenterology.

[13]  P. Robinson,et al.  Gastric mucosal cytokine and epithelial cell responses to Helicobacter pylori infection in Mongolian gerbils , 2004, The Journal of pathology.

[14]  D. Graham,et al.  Cyclooxygenase Expression During Helicobacter pylori Infection in Mongolian Gerbils , 2003, Digestive Diseases and Sciences.

[15]  F. Gao,et al.  Helicobacter pylori stimulates host cyclooxygenase‐2 gene transcription: critical importance of MEK/ERK‐dependent activation of USF1/‐2 and CREB transcription factors , 2003, Cellular microbiology.

[16]  D. Graham,et al.  Helicobacter pylori infection in mice: Role of outer membrane proteins in colonization and inflammation. , 2002, Gastroenterology.

[17]  T. Koji,et al.  Enhanced Expression of Transcription Factor E2F in Helicobacter pylori‐infected Gastric Mucosa , 2002, Helicobacter.

[18]  Y. Shiratori,et al.  Distinct Mechanism of Helicobacter pylori-mediated NF-κB Activation between Gastric Cancer Cells and Monocytic Cells* , 2001, The Journal of Biological Chemistry.

[19]  K. Fukunaga,et al.  Neuroprotective Effect of Sodium Orthovanadate on Delayed Neuronal Death after Transient Forebrain Ischemia in Gerbil Hippocampus , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  H. Höfler,et al.  Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue. , 2001, The American journal of pathology.

[21]  Y. Shiratori,et al.  Virulence Factors of Helicobacter pylori Responsible for Gastric Diseases in Mongolian Gerbil , 2000, The Journal of experimental medicine.

[22]  C. Sommer,et al.  Temporary changes of the AP-1 transcription factor binding activity in the gerbil hippocampus after transient global ischemia, and ischemic tolerance induction 1 1 Published on the World Wide Web on 22 June 2000. , 2000, Brain Research.

[23]  D. Graham,et al.  A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[24]  K. Nozaki,et al.  Activation of Mitogen-Activated Protein Kinases after Transient Forebrain Ischemia in Gerbil Hippocampus , 2000, The Journal of Neuroscience.

[25]  S. Spicer,et al.  Distribution of IκB Proteins in Gastric Mucosa and Other Organs of Mouse and Gerbil , 2000, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[26]  Yoshio Yamaoka,et al.  Cytokine Expression and Production by Purified Helicobacter pylori Urease in Human Gastric Epithelial Cells , 2000, Infection and Immunity.

[27]  K. Domanska-Janik,et al.  AP1 transcriptional factor activation and its relation to apoptosis of hippocampal CA1 pyramidal neurons after transient ischemia in gerbils , 1999, Journal of neuroscience research.

[28]  S. Kawasaki,et al.  Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and gastric ulcer in Mongolian gerbils. , 1999, The American journal of pathology.

[29]  A. Mitani,et al.  Correlation between potentiation of AP1 DNA binding and expression of c-Fos in association with phosphorylation of CREB at serine133 in thalamus of gerbils with ischemia , 1998, Brain Research.

[30]  H. Nagai,et al.  Helicobacter pylori infection induces gastric cancer in mongolian gerbils. , 1998, Gastroenterology.

[31]  N. Dyson.  The regulation of E2F by pRB-family proteins. , 1998, Genes & development.

[32]  E. Schaefer,et al.  Activation of p38MAPK in Microglia After Ischemia , 1998, Journal of neurochemistry.

[33]  R. Garofalo,et al.  A promoter recruitment mechanism for tumor necrosis factor-alpha-induced interleukin-8 transcription in type II pulmonary epithelial cells. Dependence on nuclear abundance of Rel A, NF-kappaB1, and c-Rel transcription factors. , 1998, The Journal of biological chemistry.

[34]  R. Garofalo,et al.  A Promoter Recruitment Mechanism for Tumor Necrosis Factor-α-induced Interleukin-8 Transcription in Type II Pulmonary Epithelial Cells , 1998, The Journal of Biological Chemistry.

[35]  Y. Yamaoka,et al.  Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains , 1997, Gut.

[36]  D. Beall.  Classification and Grading of Gastritis: The Updated Sydney System , 1997 .

[37]  F. Hirayama,et al.  Establishment of gastric Helicobacter pylori infection in Mongolian gerbils. , 1996, Journal of gastroenterology.

[38]  M F Dixon,et al.  Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. , 1996, The American journal of surgical pathology.

[39]  Y. Yamaoka,et al.  Helicobacter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa. , 1996, Gastroenterology.

[40]  T. Maity,et al.  Ubiquitous expression of the 43- and 44-kDa forms of transcription factor USF in mammalian cells. , 1994, Nucleic acids research.

[41]  M. Naumann,et al.  Helicobacter pylori-induced epithelial cell signalling in gastric carcinogenesis. , 2004, Trends in microbiology.

[42]  M. Washington,et al.  Activation of (cid:1) -catenin by carcinogenic Helicobacter pylori , 2022 .