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Updated: Jun 12, 2026
One-step Negative Chromatographic Purification of Helicobacter pylori Neutrophil-activating Protein Overexpressed in Escherichia coli in Batch Mode
Published on: June 18, 2016
Helicobacter pylori dupA is polymorphic, and its active form induces proinflammatory cytokine secretion by
Nawfal R Hussein1, Richard H Argent, Christian K Marx
1Nottingham Digestive Diseases Centre Biomedical Research Unit, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom.
Background:
Infection with Helicobacter pylori possessing a newly described virulence factor--duodenal ulcer-promoting gene A (dupA)--has been associated with duodenal ulceration and increased gastric inflammation.
Methods:
The dupA locus of 34 strains was sequenced. A panel of dupA mutants was generated and cocultured with human gastric epithelial cells and peripheral blood mononuclear cells; proinflammatory cytokine release was measured. IL8 expression was measured in human gastric biopsy specimens and related to the dupA and cagA status of infecting strains.
Results:
Most H. pylori strains had a dupA allele that was longer (1884 bp; dupA1) than previously described dupA alleles, although some had truncated versions (dupA2). Unlike the best-characterized H. pylori virulence determinant, the cag pathogenicity island (cag PaI), neither dupA type induced release of interleukin (IL)-8 from gastric epithelial cells. However, infections due to dupA-positive strains were associated with higher-level mucosal IL-8 messenger RNA expression in the human stomach than were infections due to dupA-negative strains. To explain this paradox, we found that dupA1 (but not dupA2 or the cag PaI) substantially increased H. pylori-induced IL-12p40 and IL-12p70 production from CD14(+) mononuclear cells. Other T helper 1-associated cytokines were also modestly induced.
Conclusion:
We suggest that virulent H. pylori strains cause inflammation by stimulating epithelial cells through cag-encoded proteins and mononuclear inflammatory cells through dupA1 products.
Insights
Helicobacter pylori strains with the duodenal ulcer-promoting gene A (dupA) stimulate inflammation. The dupA1 variant specifically enhances interleukin-12 production by immune cells, contributing to gastric inflammation.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Helicobacter pylori infection is linked to duodenal ulcers and gastric inflammation.
- The duodenal ulcer-promoting gene A (dupA) is a newly identified virulence factor.
Purpose of the Study:
- To investigate the role of the dupA gene in H. pylori-induced inflammation.
- To determine the specific mechanisms by which dupA influences cytokine production.
Main Methods:
- Sequencing of the dupA locus in 34 H. pylori strains.
- Generation of dupA mutants for coculture assays with human cells.
- Measurement of proinflammatory cytokine release and IL8 expression in gastric biopsy specimens.
Main Results:
- Two dupA variants, dupA1 (1884 bp) and dupA2 (truncated), were identified.
- Neither dupA type directly induced IL-8 release from gastric epithelial cells.
- dupA1 significantly increased H. pylori-induced IL-12 production from mononuclear cells, correlating with higher mucosal IL-8 mRNA in vivo.
Conclusions:
- H. pylori induces inflammation via distinct mechanisms: cag-encoded proteins target epithelial cells, while dupA1 products target mononuclear cells.
- The dupA1 gene is a key factor in stimulating specific immune responses contributing to gastric inflammation.
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