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

By Jung Mogg Kim, Joo Sung Kim, Jin Young Lee, Young-Suk Sim, Yu-Kyoung Oh, Ju Seop Kang, Nayoung Kim, Sunil Kim, Hyun Chae Jung, Jeehee Youn, Ho Joo Yoon and Young-Jeon Kim


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.Franchi L, 2009, NAT IMMUNOL, V10, P241, DOI 10.1038/ni.1703Shen ZJ, 2009, NAT IMMUNOL, V10, P257, DOI 10.1038/ni.1697Bergsbaken T, 2009, NAT REV MICROBIOL, V7, P99, DOI 10.1038/nrmicro2070Lee JY, 2009, J MOL MED-JMM, V87, P169, DOI 10.1007/s00109-008-0415-2Friboulet L, 2008, NEOPLASIA, V10, P1183, DOI 10.1593/neo.08590Piazuelo MB, 2008, HUM PATHOL, V39, P1360, DOI 10.1016/j.humpath.2008.01.012Kim JM, 2008, EUR J IMMUNOL, V38, P2190, DOI 10.1002/eji.200838191Wong WWL, 2008, IUBMB LIFE, V60, P390, DOI 10.1002/iub.51Hogan SP, 2008, CLIN EXP ALLERGY, V38, P709, DOI 10.1111/j.1365-2222.2008.02958.xKim JM, 2008, LAB INVEST, V88, P541, DOI 10.1038/labinvest.2008.16KNUDSON CM, 2008, METH MOL B, V414, P95Mueller S, 2008, BEST PRACT RES CL GA, V22, P425, DOI 10.1016/j.bpg.2007.12.008Lee JY, 2007, J MOL MED-JMM, V85, P1393, DOI 10.1007/s00109-007-0237-7Sheng G, 2007, AM J PHYSIOL-GASTR L, V293, pG599, DOI 10.1152/ajpgi.00182.2007Wilson KT, 2007, GASTROENTEROLOGY, V133, P288, DOI 10.1053/j.gastro.2007.05.008Kim JM, 2007, INFECT IMMUN, V75, P3373, DOI 10.1128/IAI.01940-06Gomez-Lazaro M, 2007, MOL PHARMACOL, V71, P736, DOI 10.1124/mol.106.030718Kempkensteffen C, 2007, INT J CANCER, V120, P1081, DOI 10.1002/ijc.22416Antignani A, 2006, CURR OPIN CELL BIOL, V18, P685, DOI 10.1016/ E, 2006, BBA-BIOENERGETICS, V1757, P1301, DOI 10.1016/j.bbabio.2006.05.032Kim JM, 2006, EUR J IMMUNOL, V36, P2446, DOI 10.1002/eji.200535808Kusters JG, 2006, CLIN MICROBIOL REV, V19, P449, DOI 10.1128/CMR.00054-05Yamasaki E, 2006, J BIOL CHEM, V281, P11250, DOI 10.1074/jbc.M509404200Lu H, 2005, CURR OPIN GASTROEN, V21, P653Gauthier NC, 2005, MOL BIOL CELL, V16, P4852, DOI 10.1091/mbc.E05-05-0398Li DWC, 2005, MOL BIOL CELL, V16, P4437, DOI 10.1091/mbc.E05-01-0010Vaux DL, 2005, CELL DEATH DIFFER, V12, P1205, DOI 10.1038/sj.cdd.4401696Kim JM, 2005, EUR J IMMUNOL, V35, P2648, DOI 10.1002/eji.200526321Nakayama M, 2004, J BIOL CHEM, V279, P7024, DOI 10.1074/jbc.M308898200VAN LA, 2004, FASEB J, V18, P1946Adams JM, 2003, GENE DEV, V17, P2481, DOI 10.1101/gad.1126903Nishihara H, 2003, P NATL ACAD SCI USA, V100, P8921, DOI 10.1073/pnas.1533221100Yang YL, 2003, FASEB J, V17, P790KIM JM, 2003, AM J PHYSIOL-GASTR L, V285, P1171Brito GAC, 2002, J INFECT DIS, V186, P1438Kalia N, 2002, GUT, V51, P641Salvesen GS, 2002, NAT REV MOL CELL BIO, V3, P401, DOI 10.1038/nrm830Dewson G, 2001, BLOOD, V98, P2239Kim JM, 2001, CLIN EXP IMMUNOL, V123, P421Gao LY, 2000, TRENDS MICROBIOL, V8, P306, DOI 10.1016/S0966-842X(00)01784-4Erjefalt JS, 2000, AM J RESP CRIT CARE, V161, P2074Tepes B, 1999, J PATHOL, V188, P24Kim JM, 1998, J CLIN INVEST, V102, P1815Kodama K, 1998, J GASTROENTEROL, V33, P14Rudi J, 1998, J CLIN MICROBIOL, V36, P944Gon S, 1997, J LEUKOCYTE BIOL, V62, P309Kroemer G, 1997, NAT MED, V3, P614Hatz RA, 1996, SCAND J GASTROENTERO, V31, P222DEBERNARD M, 1995, J BIOL CHEM, V270, P23937GENTA RM, 1993, MODERN PATHOL, V6, P281MCGOVERN TW, 1991, DIGEST DIS SCI, V36, P435

Topics: Apoptosis, H. pylori vacuolating cytotoxin, Eosinophils
Year: 2010
DOI identifier: 10.1002/eji.200939882
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