RT Journal Article SR Electronic T1 Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype. JF Journal of Clinical Pathology JO J Clin Pathol FD BMJ Publishing Group Ltd and Association of Clinical Pathologists SP 41 OP 45 DO 10.1136/jcp.48.1.41 VO 48 IS 1 A1 J E Crabtree A1 A Covacci A1 S M Farmery A1 Z Xiang A1 D S Tompkins A1 S Perry A1 I J Lindley A1 R Rappuoli YR 1995 UL http://jcp.bmj.com/content/48/1/41.abstract AB 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.