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 e xpressed the Toll-like receptor 4 and were sensitive to H. pylori LPS as we ll as Escherichia coli LPS. H. pylori LPS stimulated phosphorylation of tra nsforming growth factor-beta -activated kinase 1 (TAK1), TAK1-binding prote in 1 (TAB1), and c-Jun NH2-terminal kinase (JNK) 2. H. pylori LPS at >2.1 e ndotoxin unit/ml (>1 ng/ml) activated caspase-8, stimulated cytochrome c re lease from mitochondria, and subsequently activated caspases-9 and -3, lead ing to apoptosis. Epidermal growth factor blocked all of these apoptotic pr ocesses and inhibited apoptosis, whereas it did not modify the phosphorylat ion 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 mit ochondria may play crucial roles in H. pylori LPS-induced apoptosis and tha t this accelerated apoptosis may be involved in abnormal cell turnover of H . pylori-infected gastric mucosa.