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Dual effects of Helicobacter pylori vacuolating cytotoxin on human eosinophil apoptosis in early and late periods of stimulation

Cited 14 time in Web of Science Cited 19 time in Scopus
Authors
Kim, Jung Mogg; Kim, Joo Sung; Lee, Jin Young; Sim, Young-Suk; Oh, Yu-Kyoung; Kang, Ju Seop; Kim, Nayoung; Kim, Sunil; Jung, Hyun Chae; Youn, Jeehee; Yoon, Ho Joo; Kim, Young-Jeon
Issue Date
2010-06
Publisher
WILEY-V C H VERLAG GMBH
Citation
EUROPEAN JOURNAL OF IMMUNOLOGY; Vol.40 6; 1651-1662
Keywords
ApoptosisH. pylori vacuolating cytotoxinEosinophils
Abstract
Although Helicobacter pylori infections of the gastric mucosa are characterized by the infiltration of inflammatory cells such as eosinophils, the responses of eosinophils to H. pylori vacuolating cytotoxin (VacA) have not been fully elucidated. This study investigates the role of VacA in the apoptosis of human eosinophils. We treated human eosinophils with purified H. pylori VacA and observed that induction of apoptosis is a relatively late event. Expression of cellular inhibitor of apoptosis protein (c-IAP)-2 was upregulated during the early period of VacA stimulation, and transfection with c-IAP2 siRNA augmented apoptotic cell death. VacA caused the translocation of cytoplasmic Bax to the mitochondria and increased cytochrome c release from mitochondria in eosinophils. Transfection of an EoL-1 eosinophil cell line with Bax siRNA decreased the release of cytochrome c and DNA fragmentation. Furthermore, apoptosis facilitated by Bax and cytochrome c was primarily regulated by p38 MAPK in VacA-treated eosinophils. These results suggest that the exposure of human eosinophils to H. pylori VacA induces the early upregulation of c-IAP2 and a relatively late apoptotic response, with the apoptosis progressing through a sequential pathway that includes p38 MAPK activation, Bax translocation, and cytochrome c release.
ISSN
0014-2980
Language
English
URI
https://hdl.handle.net/10371/76521
DOI
https://doi.org/10.1002/eji.200939882
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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