Ex vivo nicotine stimulation augments the efficacy of human peripheral blood mononuclear cell-derived dendritic cell vaccination via activating Akt-S6 pathway.
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.
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Yan Yan
YY
Wang
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Yi Wen
YW
Yang
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Xiang
X
You
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Xiao Qian
XQ
Deng
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Chun Fang
CF
Hu
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Cong
C
Zhu
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Jun Yao
JY
Wang
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Jiao Jiao
JJ
Gu
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Yi Nan
YN
Wang
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China.
Qing
Q
Li
Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361102, China ; The State Key Laboratory for Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200032, China.
Feng Guang
FG
Gao
D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D010047:Ovalbumin / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D038601:Ribosomal Protein S6 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013347:Subcellular Fractions / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014611:Vaccination
D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D038601:Ribosomal Protein S6; D018664:Interleukin-12; D009538:Nicotine; D010047:Ovalbumin; D051057:Proto-Oncogene Proteins c-akt