Helicobacter pylori lipopolysaccharide induces apoptosis of cultured guinea pig gastric mucosal cells.
Helicobacter pylori lipopolysaccharide (LPS) is generally accepted as a low-toxicity virulence. Primary cultures of guinea pig gastric mucosal cells expressed the Toll-like receptor 4 and were sensitive to H. pylori LPS as well as Escherichia coli LPS. H. pylori LPS stimulated phosphorylation of transforming growth factor-beta-activated kinase 1 (TAK1), TAK1-binding protein 1 (TAB1), and c-Jun NH(2)-terminal kinase (JNK) 2. H. pylori LPS at >2.1 endotoxin unit/ml (>1 ng/ml) activated caspase-8, stimulated cytochrome c release from mitochondria, and subsequently activated caspases-9 and -3, leading to apoptosis. Epidermal growth factor blocked all of these apoptotic processes and inhibited apoptosis, whereas it did not modify the phosphorylation of TAK1, TAB1, and JNK2. A comparatively specific inhibitor of caspase-8 or -9 blocked apoptosis, whereas cytochrome c release was prevented only with a caspase-8-like inhibitor. Our results suggest that caspase-8 and mitochondria may play crucial roles in H. pylori LPS-induced apoptosis and that this accelerated apoptosis may be involved in abnormal cell turnover of H. pylori-infected gastric mucosa.
Kawahara
T
T
Department of Nutrition, School of Medicine, University of Tokushima, Tokushima 770-8503, Japan.
Teshima
S
S
Kuwano
Y
Y
Oka
A
A
Kishi
K
K
Rokutan
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D029721:Drosophila Proteins; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004926:Escherichia coli; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D006168:Guinea Pigs; D016480:Helicobacter pylori; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors
D003574:Cytochrome c Group; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D004815:Epidermal Growth Factor; D020169:Caspases