A secreted/shed product of Helicobacter pylori activates transcription factor nuclear factor-kappa B.
Helicobacter pylori is an etiologic agent in the development of chronic gastritis, duodenal ulceration, and gastric adenocarcinoma. Exposure of gastric epithelial cells to H. pylori induces secretion of the cytokine IL-8, which plays a pivotal role in the immunopathogenesis of H. pylori infections. Isolated Helicobacter strains differ in their virulence and in their ability to induce cytokine production. High degrees of virulence correlate with enhanced IL-8 production. However, the molecular mechanism of this variance in Helicobacter pathogenicity remains poorly understood. Here we show that H. pylori-mediated IL-8 secretion requires activation of the transcription factor nuclear factor-kappaB (NF-kappaB) in a gastric epithelial cell line. Several H. pylori strains which fail to induce IL-8 secretion do not activate NF-kappaB, while all IL-8-inducing strains activate the transcription factor. Moreover, the antioxidant curcumin, which inhibits NF-kappaB activation, also completely suppresses IL-8 induction by H. pylori. NF-kappaB activation is not mediated by LPSs, since purified H. pylori LPS had no effect on gastric epithelial cells. In contrast, both IL-8 secretion and NF-kappaB activation require a secreted H. pylori product, which is not secreted by strains mutated in picB/cagE, a recently identified putative transport protein.
Münzenmaier
A
A
Institute for Experimental Cancer Research, Tumor Biology Center, Freiburg, Germany.
Lange
C
C
Glocker
E
E
Covacci
A
A
Moran
A
A
Bereswill
S
S
Baeuerle
P A
PA
Kist
M
M
Pahl
H L
HL
D000975:Antioxidants / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism* / Q000502:physiology; D003474:Curcumin / Q000494:pharmacology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D019073:HT29 Cells; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D001426:Bacterial Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D003474:Curcumin