Roles of tumor necrosis factor-alpha-receptor type 1 and Fas in the Helicobacter pylori-induced apoptosis of gastric epithelial cells.
OBJECTIVE
Helicobacter pylori (HP) infection has been reported to accelerate the apoptosis of gastric epithelial cells. This bacteria has also been known to enhance the expression levels of molecules such as Fas antigen and a receptor for tumor necrosis factor-alpha-receptor type 1 (TNF-R1). However, whether Fas and/or TNF-R1 is actually involved in HP-mediated apoptosis has yet to be evaluated. The purpose of this study was therefore to examine the roles of Fas and TNF-R1 in HP-mediated apoptosis.


METHODS
Biopsy samples were collected from 10 HP-negative healthy volunteers and from 39 HP-positive ulcer patients. Gastric epithelial cells were obtained from the samples. The cells were then stained with anti-Fas, anti-TNF-R1 and Annexin V, which detected apoptotic cells. The findings were analyzed by three-color flow cytometry.


RESULTS
The percentages of apoptotic cells were significantly higher in HP-positive patients than in the controls. In HP-negative controls, almost all of the apoptotic cells lacked both Fas and TNF-R1. On the other hand, in HP-positive patients, HP upregulated the expression levels of Fas and TNF-R1 and, consequently, enhanced the apoptosis mediated by receptors such as Fas and TNF-R1. However, even in HP-positive patients, apoptosis was also observed in the cells that lacked both Fas and TNF-R1.


CONCLUSIONS
Fas and TNF-R1 expressed on gastric epithelial cells from HP-infected patients were responsible for the accelerated apoptosis of the cells.
Hasumi
Keizo
K
Department of Infectious Diseases, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
Tanaka
Kazuo
K
Saitoh
Shin
S
Takagi
Atsushi
A
Miwa
Takeshi
T
Mine
Tetsuya
T
Koga
Yasuhiro
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000502:physiology; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology*; D016481:Helicobacter Infections / Q000473:pathology / Q000503:physiopathology*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D019014:fas Receptor / Q000502:physiology*
D017304:Annexin A5; D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D019014:fas Receptor