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Medline ® Abstract for Reference 67

of 'Pathophysiology of and immune response to Helicobacter pylori infection'

Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype.
Crabtree JE, Covacci A, Farmery SM, Xiang Z, Tompkins DS, Perry S, Lindley IJ, Rappuoli R
J Clin Pathol. 1995;48(1):41.
AIMS: To use a range of natural phenotypically variant strains of Helicobacter pylori with disparate CagA and VacA (vacuolating cytotoxin) expression to determine which bacterial factors are more closely associated with epithelial interleukin-8 (IL-8) induction.
METHODS: Gastric epithelial cells (AGS and KATO-3) were co-cultured with five H pylori strains which were variously shown to express the cagA gene/CagA protein, VacA and/or to exhibit biological cytotoxicity. Secreted IL-8 was assayed by enzyme leaked immunosorbent assay (ELISA) and IL-8 messenger RNA (mRNA) was assayed using a reverse transcription polymerase chain reaction based technique (RT-PCR).
RESULTS: Strains expressing CagA, including a variant strain (D931) which is non-cytotoxic and does not express the VacA protein, were found to upregulate epithelial IL-8 secretion and gene expression. In contrast, strains with no CagA expression, even in the presence of VacA and/or biological cytotoxicity, (G104, BA142), failed to induce IL-8 protein or mRNA above control values.
CONCLUSIONS: These results strongly support a role for H pylori CagA or coexpressed factors other than the cytotoxin in upregulation of gastric epithelial IL-8. Increased epithelial IL-8 secretion and concomitant neutrophil chemotaxis and activation in addition to direct cytotoxicity may be an important factor in tissue damage and ulceration.
Department of Clinical Medicine, St James's University Hospital, Leeds.