title: Nicotine stimulated bone marrow-derived dendritic cells could augment HBV specific CTL priming by activating PI3K-Akt pathway.
abstract: Our previous studies have revealed that nicotine-treated immature dendritic cells (imDCs) have anti-tumor effects in murine lymphoma models. The present study is to explore HBV-specific CTL priming and its cytolytic activities of nicotine-treated murine DCs, the mechanism of α7 nicotinic acetylcholine receptor (nAChR) up-regulation by nicotine and the efficiency of nicotine with other cytokines. To address these hypotheses, bone marrow-derived imDCs were stimulated by nicotine and expression of α7 nAChR was firstly determined by flow cytometry and Western blot. Then, DCs-dependent HBV-specific T cell proliferation and IL-12 secretion were secondly determined by BrdU cell proliferation assay and ELISA, respectively. The HBV-specific CTL priming and its activities were further explored by intraperitoneal transfer of nicotine treated imDCs. The mechanism of nicotine up-regulating α7 nAChR was finally explored by Western blot. The results showed that: first, the maximal activation of PI3K and Akt was reached at 30 and 60-120 min respectively after nicotine stimulation. Nicotine up-regulated the expression of α7 nAChR by activating PI3K-Akt pathway in murine DCs; secondly, nicotine stimulation could enhance DCs' ability of HBV-specific T cell proliferation and IL-12 secretion; thirdly, adoptive transfer of nicotine stimulated DCs could induce HBV specific CTL priming in vivo and those CTL had cytolytic activities; fourthly, nicotine had equal efficiencies to 2 ng/ml IFN-γ in DCs-mediated T cell proliferation. All these data presented here indicated that nicotine treated imDCs might be considered as a potential candidate for HBV immunotherapy.
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China.
authors.forename: Hao Jie
authors.initials: HJ
authors.lastname: Jin
authors.forename: Hai Tao
authors.initials: HT
authors.lastname: Li
authors.forename: Hua Xiu
authors.initials: HX
authors.lastname: Sui
authors.forename: Mao Qiang
authors.initials: MQ
authors.lastname: Xue
authors.forename: Yi Nan
authors.initials: YN
authors.lastname: Wang
authors.forename: Jia Xun
authors.initials: JX
authors.lastname: Wang
authors.forename: Feng Guang
authors.initials: FG
authors.lastname: Gao
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy; D006511:Hepatitis B Antigens / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; D006511:Hepatitis B Antigens; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D018664:Interleukin-12; D009538:Nicotine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt