Nicotine Up-regulated 4-1BBL Expression by Activating Mek-PI3K Pathway Augments the Efficacy of Bone Marrow-Derived Dendritic Cell Vaccination | |
Jin, Hao Jie ; Sui, Hua Xiu ; Wang, Yi Nan ; Gao, Feng Guang ; Gao FG(高丰光) | |
刊名 | http://dx.doi.org/10.1007/s10875-012-9761-5
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2013 | |
关键词 | HUMAN T-CELLS EFFECTOR FUNCTION CANCER CELLS COSTIMULATION LIGAND IMMUNITY FAMILY LUNG PROLIFERATION GENERATION |
英文摘要 | Natural Science Foundation of Xiamen [3502Z20104002]; Natural Science Foundation of China; National Laboratory for Oncogenes and Related Genes of China [90-08-02]; Purpose To explore the role of 4-1BBL in nicotine-treated immature dendritic cells (imDCs) mediated anti-tumor effects. Methods Bone marrow-derived imDCs were stimulated with nicotine and 4-1BBL expression was determinated by flow cytometry, Western blot and RT-PCR respectively. Then, the roles of 4-1BBL in nicotine-augmented DCs-dependent T cell proliferation, CTL priming and antitumor effects were investigated by BrdU cell proliferation assay, enzyme-linked immunospot assay and in vivo preventive effect on tumor development, respectively. Finally, using relative kinase inhibitors, the mechanism of 4-1BBL up-regulation by nicotine stimulation and the roles of Mek-PI3K signal pathways in nicotine-augmented DCs-dependent T cell proliferation were explored by Western blot and BrdU cell proliferation assay, respectively. Results Firstly, nicotine could up-regulate 4-1BBL expression in both protein and mRNA levels. Secondly, the effects of nicotine-augmented DCs-dependent T-cell proliferation, CTL priming and anti-tumor effects could be significantly abolished by blocking CD80, CD86 and 4-1BBL activity, respectively. Thirdly, the combined blockages of CD80/CD86, CD80/4-1BBL, CD86/4-1BBL or CD80/CD86/4-1BBL signals could decrease 53.2 %, 29.6 %, 27.9 % and 54.5 % nicotine-enhanced T cell proliferation, respectively. Importantly, nicotine-induced 4-1BBL up-regulation could be decreased by the usage of Mek-PI3K pathway kinase inhibitors. The pre-treatment of Mek-p38-PI3K kinase inhibitors could obviously abolish nicotine-augmented DCs-dependent T cell proliferation. Conclusions CD80/CD86 and 4-1BBL are critical for nicotine augmented DCs-mediated anti-tumor effects. 4-1BBL and CD80/CD86 could be considered as potential candidates for preventive and therapeutic tumor vaccination. |
语种 | 英语 |
出版者 | SPRINGER/PLENUM PUBLISHERS |
内容类型 | 期刊论文 |
源URL | [http://dspace.xmu.edu.cn/handle/2288/93429] ![]() |
专题 | 医学院-已发表论文 |
推荐引用方式 GB/T 7714 | Jin, Hao Jie,Sui, Hua Xiu,Wang, Yi Nan,et al. Nicotine Up-regulated 4-1BBL Expression by Activating Mek-PI3K Pathway Augments the Efficacy of Bone Marrow-Derived Dendritic Cell Vaccination[J]. http://dx.doi.org/10.1007/s10875-012-9761-5,2013. |
APA | Jin, Hao Jie,Sui, Hua Xiu,Wang, Yi Nan,Gao, Feng Guang,&高丰光.(2013).Nicotine Up-regulated 4-1BBL Expression by Activating Mek-PI3K Pathway Augments the Efficacy of Bone Marrow-Derived Dendritic Cell Vaccination.http://dx.doi.org/10.1007/s10875-012-9761-5. |
MLA | Jin, Hao Jie,et al."Nicotine Up-regulated 4-1BBL Expression by Activating Mek-PI3K Pathway Augments the Efficacy of Bone Marrow-Derived Dendritic Cell Vaccination".http://dx.doi.org/10.1007/s10875-012-9761-5 (2013). |
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