title: Helicobacter pylori activates NF-kappaB via the alternative pathway in B lymphocytes.
abstract: Helicobacter pylori causes various gastroduodenal diseases including gastric MALT lymphoma, but the mechanism underlying H. pylori-induced carcinogenesis is not known. The alternative pathway for NF-kappaB activation, which involves the processing of NF-kappaB2/p100 to p52, has been implicated in lymphocyte survival, attenuated apoptosis, and secondary lymphoid tissue development. In this study, we investigated H. pylori-induced activation of NF-kappaB through the alternative pathway in B lymphocytes. In immunoblot and EMSA, H. pylori induced NF-kappaB2/p100 processing to p52 and subsequent nuclear accumulation in IM-9 (human B cell line) cells and human peripheral blood B cells, but not in AGS (human gastric cancer cell line) cells. The activation of the alternative pathway was LPS-dependent but not cag pathogenicity island-dependent. Alternative pathway activation by H. pylori was associated with attenuated apoptosis. The expression levels of B lymphocyte chemoattractant, EBI-1 ligand chemokine, and stromal cell-derived factor-1alpha mRNAs were up-regulated in cocultured human B cells and in infected human gastric mucosa. In the infected mucosa, NF-kappaB2/p100 and p52 were detected immunohistochemically in the cytoplasm and nuclear compartments of lymphocytes, but not in epithelial cells. In summary, H. pylori activates the alternative NF-kappaB pathway in B lymphocytes. The effects on chemokine production and antiapoptosis mediated by H. pylori-induced processing of NF-kappaB2/p100 to p52 may drive lymphocytes to acquire malignant potential.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Hongo, Tokyo, Japan. tohmae-tky@umin.ac.jp
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ohmae
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hirata
authors.forename: Shin
authors.initials: S
authors.lastname: Maeda
authors.forename: Wataru
authors.initials: W
authors.lastname: Shibata
authors.forename: Ayako
authors.initials: A
authors.lastname: Yanai
authors.forename: Keiji
authors.initials: K
authors.lastname: Ogura
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Takao
authors.initials: T
authors.lastname: Kawabe
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000096:biosynthesis / Q000276:immunology; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology; D018920:Coculture Techniques; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C515460:CCL19 protein, human; C515255:CXCL12 protein, human; C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D012333:RNA, Messenger