Helicobacter pylori activates NF-kappaB via the alternative pathway in B lymphocytes.
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.
Ohmae
Tomoya
T
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Hongo, Tokyo, Japan. tohmae-tky@umin.ac.jp
Hirata
Yoshihiro
Y
Maeda
Shin
S
Shibata
Wataru
W
Yanai
Ayako
A
Ogura
Keiji
K
Yoshida
Haruhiko
H
Kawabe
Takao
T
Omata
Masao
M
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
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