Helicobacter pylori induces IkappaB kinase alpha nuclear translocation and chemokine production in gastric epithelial cells.
NF-kappaB is an important transcriptional factor that is involved in multiple cellular responses, such as inflammation and antiapoptosis. IkappaB kinase alpha (IKKalpha) and IKKbeta, which are critical regulators of NF-kappaB activity, possess various mechanisms for NF-kappaB activation. This variability in NF-kappaB signaling may be associated with distinct inflammatory responses in specific cell types. The gastric pathogen Helicobacter pylori is known to activate NF-kappaB. However, the role of IKK in H. pylori infection remains unclear. In this report, we show that H. pylori activates both IKKalpha and IKKbeta in gastric cancer cells and enhances NF-kappaB signaling in distinct manners. We found that IKKbeta acted as an IkappaBalpha kinase during H. pylori infection, whereas IKKalpha did not. H. pylori induced IKKalpha nuclear translocation in time-, multiplicity of infection-, and cag pathogenicity island-dependent manners. In contrast, p100 processing, which is a known IKKalpha activity induced by several cytokines, was not induced by H. pylori. Both IKKs were responsible for chemokine secretion by infected cells. However, the antiapoptotic effect of H. pylori was merely transduced by IKKbeta. Microarray analysis and real-time PCR indicated that both IKKs were involved in the transcriptional activation of genes associated with inflammation, antiapoptosis, and signal transduction. Our results indicate that H. pylori activates NF-kappaB via both IKKalpha and IKKbeta using distinct mechanisms. IKKalpha nuclear translocation induced by H. pylori is indispensable for appropriate inflammatory responses but not for antiapoptosis, which suggests a critical role for IKKalpha in gastritis development.
Hirata
Yoshihiro
Y
Department of Gastroenterology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. yohirata-tky@umin.ac.jp
Maeda
Shin
S
Ohmae
Tomoya
T
Shibata
Wataru
W
Yanai
Ayako
A
Ogura
Keiji
K
Yoshida
Haruhiko
H
Kawabe
Takao
T
Omata
Masao
M
D018925:Chemokines; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000096:biosynthesis* / Q000378:metabolism*; D046228:Microarray Analysis; D013270:Stomach / Q000166:cytology
D018925:Chemokines; D051550:I-kappa B Kinase