title: Induction of cell signaling events by the cholera toxin B subunit in antigen-presenting cells.
abstract: Cholera toxin (CT) is one of the most effective and widely studied mucosal adjuvants. Although the ADP-ribosylating A subunit has been implicated in augmenting immune responses, the receptor-binding B subunit (CT-B) has greater immunogenicity and may be a repository of adjuvant activity without potential toxicity. In order to elucidate mechanisms of immune modulation by CT-B alone, primary B cells and macrophages were assessed for responses to CT-B in vitro, as measured by the expression of cell surface markers, cellular signaling events, and cytokine secretion. Increased phosphorylation of multiple signaling molecules, including Erk1/2 and p38, was detected. CT-B also induced transactivation of the transcription elements cyclic AMP-responsive element and NF-kappaB, the latter of which was inhibited by phosphotyrosine inhibition. While specific inhibition of MEK1/2 did not reduce CT-B induction of cell surface marker expression, it did attenuate CT-B-mediated interleukin-6 secretion. These data show that CT-B induces a set of signaling events related to cellular activation, surface molecule expression, and cytokine production that has potential implications for elucidating CT-B adjuvant activity in the absence of enzymatically active holotoxin.
authors.affiliation: Evans Biomedical Research Center, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA.
authors.forename: Aletta C
authors.initials: AC
authors.lastname: Schnitzler
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Burke
authors.forename: Lee M
authors.initials: LM
authors.lastname: Wetzler
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D002450:Cell Communication; D002772:Cholera Toxin / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D002772:Cholera Toxin