Helicobacter pylori induces CCL20 expression.
CCL20 attracts immature dendritic cells and memory T cells and plays a role on mucosal surfaces in inflammation. However, whether Helicobacter pylori infection induces CCL20 in human gastric epithelial cells remains to be determined. The aim of this study was to analyze the molecular mechanism of H. pylori-induced CCL20 expression. Expression of CCL20 mRNA was assessed by reverse transcription-PCR. Five normal and five H. pylori-infected gastric tissue samples were stained immunohistochemically for CCL20. A luciferase assay was used to monitor activation of the CCL20 gene promoter, and an electrophoretic mobility shift assay was used to explore the binding of transcription factors to this promoter. The CCL20 expression in epithelial cells of H. pylori-positive tissues was higher than that in H. pylori-negative tissues. H. pylori induced CCL20 expression in gastric epithelial cell lines, and the induction was dependent on an intact cag pathogenicity island. Activation of the CCL20 promoter by H. pylori occurred through the action of NF-kappaB. Transfection of IkappaB kinase and NF-kappaB-inducing kinase dominant negative mutants inhibited H. pylori-mediated activation of CCL20. Treatment with an inhibitor of Hsp90 suppressed H. pylori-induced CCL20 mRNA due to deactivation of NF-kappaB. Collectively, these results suggest that H. pylori activates NF-kappaB through an intracellular signaling pathway that involves IkappaB kinase and NF-kappaB-inducing kinase, leading to CCL20 gene transcription, and that Hsp90 is a crucial regulator of H. pylori-induced CCL20 expression, presumably contributing to the immune response in H. pylori.
Tomimori
Koh
K
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
Uema
Eriko
E
Teruya
Hiromitsu
H
Ishikawa
Chie
C
Okudaira
Taeko
T
Senba
Masachika
M
Yamamoto
Kazuo
K
Matsuyama
Toshifumi
T
Kinjo
Fukunori
F
Fujita
Jiro
J
Mori
Naoki
N
D019677:Artificial Gene Fusion; D001706:Biopsy; D002460:Cell Line; D054418:Chemokine CCL20 / Q000096:biosynthesis* / Q000235:genetics; D004269:DNA, Bacterial / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology; D017930:Genes, Reporter; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D004269:DNA, Bacterial; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors; D008156:Luciferases