title: Cholera toxin breakdowns oral tolerance via activation of canonical NF-κB.
abstract: The mechanisms of mucosal immunogenicity and adjuvanticity of bacterial exotoxins remains unknown. In this study, we investigated the role of the transcription factor nuclear factor-κB (NF-κB) in cholera toxin (CT)-induced alteration of oral tolerance. Feeding CT abrogated ovalbumin (OVA)-induced oral tolerance, as evaluated by OVA-specific serum antibody responses, and CD4(+) T cell proliferation. CT feeding activated canonical NF-κB (one heterodimer type, p50-p65) and mRNA expression of NF-κB-dependent proinflammatory cytokines in mesenteric lymph node (MLN) and Peyer's patch (PP) cells. CT no longer showed abrogation of oral tolerance in mice pretreated with p50 small interfering RNAs (siRNAs). ADP-ribosylation inhibitors inhibited CT-induced NF-κB activation. These data suggest that CT induces canonical NF-κB activation in intestinal lymphoid cells, which plays a key role in mucosal immunogenicity and adjuvanticity.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Han-A
authors.initials: HA
authors.lastname: Kim
authors.forename: Kook Heon
authors.initials: KH
authors.lastname: Seo
authors.forename: Hern-Ku
authors.initials: HK
authors.lastname: Lee
authors.forename: Bok Yun
authors.initials: BY
authors.lastname: Kang
authors.forename: Suhn-Young
authors.initials: SY
authors.lastname: Im
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics; D009536:Niacinamide / Q000494:pharmacology; D010047:Ovalbumin; D010581:Peyer's Patches / Q000276:immunology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA / Q000378:metabolism; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D007070:Immunoglobulin A; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014803:Vitamin B Complex; C073701:Nfkb1 protein, mouse; D009536:Niacinamide; C025160:3-aminobenzamide; D010047:Ovalbumin; D002772:Cholera Toxin
keywords: 3-AB; 3-aminobenzamide; 5-(and 6)-carboxyfluorescein diacetate succinimidyl ester; CFSE; CT; Cholera toxin; DC; FBS; IL; MLN; Mesenteric lymph node; NF-κB; OVA; Oral tolerance; PCR; PEI; PP; Peyer’s patch; TNF; cholera toxin; dendritic cells; fetal bovine serum; interleukin; mesenteric lymph node; nuclear factor-κB; ovalbumin; polyethylene imine; polymerase chain reaction; siRNA; small interfering RNA; tumor necrosis factor