Activation of activator protein 1 and stress response kinases in epithelial cells colonized by Helicobacter pylori encoding the cag pathogenicity island

Citation
M. Naumann et al., Activation of activator protein 1 and stress response kinases in epithelial cells colonized by Helicobacter pylori encoding the cag pathogenicity island, J BIOL CHEM, 274(44), 1999, pp. 31655-31662
Citations number
58
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
274
Issue
44
Year of publication
1999
Pages
31655 - 31662
Database
ISI
SICI code
0021-9258(19991029)274:44<31655:AOAP1A>2.0.ZU;2-B
Abstract
Helicobacter pylori interacts with the apical membrane of the gastric epith elium and induces a number of proinflammatory cytokines/chemokines. The sub sequent infiltration of macrophages and granulocytes into the mucosa leads to gastric inflammation accompanied by epithelial degeneration. Gastric dis eases, e.g peptic ulcer or gastric adenocarcinoma, are more common among pe ople infected with H, pylori strains producing VacA (vacuolating cytotoxin A) and possessing a cog (cytotoxin-associated antigen A) pathogenicity isla nd. For the induction of the cytokine/chemokine genes in response to H. pyl ori, we studied the signaling leading to the nuclear activation of the earl y response transcription factor activator protein 1 (AP-1), We found that H . pylori strains carrying the pathogenicity island induce activation of AP- 1 and nuclear factor KB, In contrast to the wild type or an isogenic strain without the vacA gene, isogenic H. pylori strains with mutations in certai n cog genes revealed only weak AP-1 and nuclear factor KB activation. In re spect to the molecular components that direct AP-1 activity, our results in dicate a cascade of the cellular stress response kinases c-Jun N-terminal k inase, MAP kinase kinase 4, and p21-activated kinase, and small Rho-GTPases including Rad and Cdc42, which contributes to the activation of proinflamm atory cytokines/chemokines induced by H. pylori encoding the cag pathogenic ity island.