Caspase-3 Activation Leads to Apoptosis of Human Gastric Epithelial Cells Infected with Helicobacter pylori

Kim, Jung Mogg; Kim, Joo Sung; Jung, Hyun Chae; Song, In Sung; Kim, Chung Yong

Abstract

BACKGROUND/AIMS: Infection with Helicobacter pylori activates a proinflammatory gene program in human gastric epithelial cells and is associated with significant epithelial cell damage. We evaluated whether H. pylori infection could increase apoptosis of gastric epithelial cells via caspase-3 activation
METHODS
After human gastric epithelial cells were infected with H. pylori, apoptosis was assessed by Hoechst staining, flow cytometric analysis, and cell death detection enzyme linked immunosorben assay. Caspase-3 activation was determined by the detection of the chromophore p-nitroanilide (pNA) after cleavage from the substrate DEVD-pNA.
RESULTS
Activation of caspase-3 was first apparent 12 hours and the phenotypic expression of apoptosis was first apparent 18 hours after H. pylori infection The addition of DEVD-fmk inhibited apoptosis of H. pylori-infected epithelial cells. The addition o TNF alpha significantly increased caspase-3 activation and apoptosis of Hs746T gastric epithelial cells infected with H. pylori. The extent of apoptosis was similar in cases of cagA+cytotoxin+, cagA+ cytotoxin- or cagA-cytotoxin- H. pylori-infected gastric epithelial cell cultures.
CONCLUSIONS
These results suggest that H. pylori can induce gastric epithelial cell apoptosis by activation of caspase-3 Furthermore, this apoptotic process can be induced directly by H. pylori and regulated by immunemediators such as TNF alpha.