Ex vivo nicotine stimulation augments the efficacy of human peripheral blood mononuclear cell-derived dendritic cell vaccination via activating Akt-S6 pathway.
Anal Cell Pathol (Amst)
; 2015: 741487, 2015.
Article
em En
| MEDLINE
| ID: mdl-26351626
ABSTRACT
Our previous studies showed that α7 nicotinic acetylcholine receptor (nAchR) agonist nicotine has stimulatory effects on murine bone marrow-derived semimature DCs, but the effect of nicotine on peripheral blood mononuclear cell- (PBMC-) derived human semimature dendritic cells (hu-imDCs) is still to be clarified. In the present study, hu-imDCs (cultured 4 days) were conferred with ex vivo lower dose nicotine stimulation and the effect of nicotine on surface molecules expression, the ability of cross-presentation, DCs-mediated PBMC priming, and activated signaling pathways were determined. We could demonstrate that the treatment with nicotine resulted in increased surface molecules expression, enhanced hu-imDCs-mediated PBMC proliferation, upregulated release of IL-12 in the supernatant of cocultured DCs-PBMC, and augmented phosphorylation of Akt and ribosomal protein S6. Nicotine associated with traces of LPS efficiently enhanced endosomal translocation of internalized ovalbumin (OVA) and increased TAP-OVA colocalization. Importantly, the upregulation of nicotine-increased surface molecules upregulation was significantly abrogated by the inhibition of Akt kinase. These findings demonstrate that ex vivo nicotine stimulation augments hu-imDCs surface molecules expression via Akt-S6 pathway, combined with increased Ag-presentation result in augmented efficacy of DCs-mediated PBMC proliferation and Th1 polarization.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Leucócitos Mononucleares
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Transdução de Sinais
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Vacinação
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Proteína S6 Ribossômica
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Proteínas Proto-Oncogênicas c-akt
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Nicotina
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article