Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype.
OBJECTIVE
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.
Crabtree
J E
JE
Department of Clinical Medicine, St James's University Hospital, Leeds.
Covacci
A
A
Farmery
S M
SM
Xiang
Z
Z
Tompkins
D S
DS
Perry
S
S
Lindley
I J
IJ
Rappuoli
R
R
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D015870:Gene Expression; D016480:Helicobacter pylori / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016209:Interleukin-8; D012333:RNA, Messenger; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori