Open AccessVacuolating Cytotoxin in Helicobacter pylori Water-Soluble Proteins Upregulates Chemokine Expression in Human Eosinophils via Ca 2+ Influx, Mitochondrial Reactive Oxygen Intermediates, and NF-κB Activation
Author(s) -
Jung Mogg Kim,
Sang Woo Kim,
Jin Young Lee,
Yeong-Jeon Kim,
Ho-Joo Youn,
In Young Kim,
Youngjoon Chee,
YuKyoung Oh,
Nayoung Kim,
Hyun Chae Jung,
In Sung Song
Publication year - 2007
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01940-06
Subject(s) - chemokine , interleukin 8 , biology , microbiology and biotechnology , helicobacter pylori , monocyte , ccl17 , immunology , inflammation , chemokine receptor , genetics
Helicobacter pylori -infected gastric mucosa is characterized by infiltration of inflammatory cells such as neutrophils and eosinophils. However, little information is available on the relationship betweenH. pylori virulence factors and chemokine expression in eosinophils. This study investigates the role of vacuolating cytotoxin (VacA) in chemokine expression from human eosinophils. Eosinophils were isolated from the peripheral blood of healthy volunteers using a magnetic cell separation system. VacA+ H. pylori water-soluble proteins (WSP) induced higher expression of interleukin-8, growth-related oncogene alpha, monocyte chemotactic protein 1, and RANTES (regulated on activation, normal, T-cell expressed and secreted) than Vac− WSP in human eosinophils, as assessed by quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. Purified VacA not only increased chemokine expression but also activated p65/p50 NF-κB heterodimers and phosphorylated IκB kinase (IKK) α/β signals in human eosinophils. Inhibition of NF-κB and IKK significantly decreased the chemokine expression in VacA-stimulated eosinophils. Furthermore, VacA-induced NF-κB activation and chemokine release from eosinophils were dependent on Ca2+ influx and mitochondrial generation of reactive oxygen intermediates (ROI). These results suggest that NF-κB and IKK signals via Ca2+ influx and mitochondrial ROI play a role in the up-regulation of chemokine expression in eosinophils stimulated withH. pylori VacA.