The effect of Helicobacter pylori on cell proliferation and apoptosis in gastric epithelial cell lines.
BACKGROUND
Helicobacter pylori has been implicated in the pathogenesis of gastric cancer and malignant lymphoma. It is not known whether the bacterium stimulates cell proliferation directly or if apoptosis induced by H. pylori leads to a hyperproliferative response.


OBJECTIVE
To clarify the precise mechanism of H. pylori action on gastric epithelial cell growth, we compared the response of two cell lines, Kato III (p53 deletion) and MKN 45 (p53 wild type), to the organism. To determine the role of Helicobacter vacuolating cytotoxin in gastric mucosal injury, we examined the relation between vacuolating activity and apoptosis under several conditions.


METHODS
Five cytotoxic and four noncytotoxic strains of H. pylori were used, each with an inoculum of 10(7) cfu/mL. The effect on the growth in MKN 45 and Kato III cells was studied by MTT assay. Vacuolating cytotoxin activity was determined using RK-13 cells.


RESULTS
Neither cytotoxic nor noncytotoxic strains induced apoptosis, but death of MKN 45 cells was induced by pre-treatment with interferon-gamma and culture with TNF-alpha. In contrast, some strains of H. pylori increased proliferation of Kato III cells. Furthermore, cell death induced by cytotoxic strains, but not noncytotoxic strains, was significantly augmented by amoxycillin 5-50 g/mL (P=0.0016). On the other hand, acid-treated supernatant fluids from cultures of H. pylori showed enhanced vacuolating activity but did not induce cell death, suggesting that death is attributable to some factor other than the cytotoxin.


CONCLUSIONS
These findings suggest that H. pylori induces apoptosis by a means independent of vacuolating cytotoxin.
Takagi
A
A
Department of Internal Medicine, Tokai University School of Medicine, Boseidai, Isehara, Japan.
Watanabe
S
S
Igarashi
M
M
Koike
J
J
Hasumi
K
K
Deguchi
R
R
Koga
Y
Y
Miwa
T
T
D017209:Apoptosis; D002455:Cell Division; D002460:Cell Line; D019610:Cytoprotection; D004847:Epithelial Cells / Q000166:cytology*; D005753:Gastric Mucosa / Q000166:cytology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma