Effect of Nuclear Factor Kappa B Decoy Oligodeoxynucleotides Transfection on Biological Characteristics of Mature Dendritic Cells in Mice_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

SUO Lijun ¹ ,  SHI Yi ¹ , ZHANG Fang ¹ , WAN Ying ² , CHEN Yongwen ² , HUANG Gang ³ , LI Ziling ¹ , SONG Yong. ¹

Department of Respiratory Medicine, Nanjing Genaral Hospital of Nanjing Military Command, Clinical School of Medical College, Nanjing University.Nanjing, Jiangsu, 210002, China;

Corresponding author：

SHI Yi, Email: shiyi56@126.com

Keywords：

Nuclear factor kappa B; Decoy oligodeoxynucleotides; Dendritic cells; Immune tolerance; Asthma

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Objective To investigate the effects of nuclear factor kappa B decoy oligodeoxynucleotides ( NF-κB decoy ODN) transfection on biological characteristics of mature dendritic cells ( mDCs) in mice. Methods Immature DCs were harvested from Balb / c mice bone marrow, followed by the incubation with antigen OVA and LPS, and mature DCs were evaluated by the expressions of CD11c and MHC-Ⅱ detected by FACS. Mature DCs were transfected with NF-κB decoy ODN and the changes of NF-κB activity after the transfection were detected by EMSA. The expressions of the costimulatory molecules( CD40,CD80 and CD86) on DCs were detected by FACS and the proliferation of T cells was tested by mixed lymphocyte reaction( MLR) . Results The mature DCs were cultured successfully. The NF-κB activity of NF-κB decoy ODN transfected DCs was decreased significantly( P lt; 0. 05) . There was no difference in the expressions of CD40 and CD80, but the expression of CD86 was decreased significantly in NF-κB decoy ODN transfection group( P lt; 0. 05) . MLR test showed that the proliferation of T lymphocyte cells was inhibited by NF-κB decoy ODN transfected DCs, but was stimulated bly by the DCs of other groups. Conclusions Mature DCs transfected with NF-κB decoy ODN could inhibit the proliferation and activation of antigenspecical T cells, which was probably related to the down-regulation of CD86 on DCs. This modified DCs might be a promising vaccine for the treatment of asthma in the future.

Citation： SUO Lijun,SHI Yi,ZHANG Fang,WAN Ying,CHEN Yongwen,HUANG Gang,LI Ziling,SONG Yong.. Effect of Nuclear Factor Kappa B Decoy Oligodeoxynucleotides Transfection on Biological Characteristics of Mature Dendritic Cells in Mice. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(3): 271-274. doi: Copy

1.	Zhou LF, Zhang MS, Hu AH, et al. Selective blockade of NF-kappaB by novel mutated IkappaBalpha suppresses CD3 / CD28-induced activation of memory CD4 + T cells in asthma. Allergy, 2008, 63 :509-517.
2.	alpha, 25 -dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-beta. J Immunol, 2008, 180: 5211-5221.
3.	Taher YA, van Esch BC, Hofman GA, et al.
4.	孙正, 许哲, 祁小平, 等. 树突状细胞-结直肠癌细胞融合疫苗的制备及生物学特性的研究. 医学研究生学报, 2006, 19: 19-22.
5.	Isomura I, Tsujimura K, Morita A. Antigen-specific peripheral tolerance induced by topical application of NF-kappaB decoy oligodeoxynucleotide. J Invest Dermatol, 2006, 126: 97-104.
6.	关键, 郑碧霞, 程德云. 核因子-κB 在慢性阻塞性肺疾病大鼠肺内的表达及泼尼松对其的影响. 中国呼吸与危重监护杂志,2008, 7: 52-56.
7.	Preciado D, Lin J, Wuertz B, et al. Cigarette smoke activates NFkappa B and induces Muc5b expression in mouse middle ear cells.Laryngoscope, 2008, 118: 464-471.
8.	Wu K, Bi Y, Sun K, et al. Suppression of allergic inflammation by allergen-DNA-modified dendritic cells depends on the induction of Foxp3 + Regulatory T cells. Scand J Immunol, 2008, 67: 140-151.
9.	Lu L, Lee WC, Takayama T, et al. Genetic engineering of dendritic cells to express immunosuppressive molecules ( viral IL-10, TGFbeta,and CTLA4Ig) . J Leukoc Biol, 1999, 66: 293-296.
10.	Liu YJ. Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell-mediated allergic inflammation. J Allergy Clin Immunol, 2007, 120: 238-244.
11.	Cruz MT, Duarte CB, Gon　alo M, et al. LPS induction of I kappa Balpha degradation and iNOS expression in a skin dendritic cell line is prevented by the janus kinase 2 inhibitor, Tyrphostin b42. Nitric Oxide, 2001 , 5: 53-61 .
12.	Thoeni G, Stoitzner P, Brandacher G, et al. Tetrahydro-4 -aminobiopterin attenuates dendritic cell-induced T cell priming independently from inducible nitric oxide synthase. J Immunol,2005, 174: 7584-7591.

1. Zhou LF, Zhang MS, Hu AH, et al. Selective blockade of NF-kappaB by novel mutated IkappaBalpha suppresses CD3 / CD28-induced activation of memory CD4 + T cells in asthma. Allergy, 2008, 63 :509-517.
2. alpha, 25 -dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-beta. J Immunol, 2008, 180: 5211-5221.
3. Taher YA, van Esch BC, Hofman GA, et al.
4. 孙正, 许哲, 祁小平, 等. 树突状细胞-结直肠癌细胞融合疫苗的制备及生物学特性的研究. 医学研究生学报, 2006, 19: 19-22.
5. Isomura I, Tsujimura K, Morita A. Antigen-specific peripheral tolerance induced by topical application of NF-kappaB decoy oligodeoxynucleotide. J Invest Dermatol, 2006, 126: 97-104.
6. 关键, 郑碧霞, 程德云. 核因子-κB 在慢性阻塞性肺疾病大鼠肺内的表达及泼尼松对其的影响. 中国呼吸与危重监护杂志,2008, 7: 52-56.
7. Preciado D, Lin J, Wuertz B, et al. Cigarette smoke activates NFkappa B and induces Muc5b expression in mouse middle ear cells.Laryngoscope, 2008, 118: 464-471.
8. Wu K, Bi Y, Sun K, et al. Suppression of allergic inflammation by allergen-DNA-modified dendritic cells depends on the induction of Foxp3 + Regulatory T cells. Scand J Immunol, 2008, 67: 140-151.
9. Lu L, Lee WC, Takayama T, et al. Genetic engineering of dendritic cells to express immunosuppressive molecules ( viral IL-10, TGFbeta,and CTLA4Ig) . J Leukoc Biol, 1999, 66: 293-296.
10. Liu YJ. Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell-mediated allergic inflammation. J Allergy Clin Immunol, 2007, 120: 238-244.
11. Cruz MT, Duarte CB, Gon　alo M, et al. LPS induction of I kappa Balpha degradation and iNOS expression in a skin dendritic cell line is prevented by the janus kinase 2 inhibitor, Tyrphostin b42. Nitric Oxide, 2001 , 5: 53-61 .
12. Thoeni G, Stoitzner P, Brandacher G, et al. Tetrahydro-4 -aminobiopterin attenuates dendritic cell-induced T cell priming independently from inducible nitric oxide synthase. J Immunol,2005, 174: 7584-7591.

Chinese Journal of Respiratory and Critical Care Medicine

Effect of Nuclear Factor Kappa B Decoy Oligodeoxynucleotides Transfection on Biological Characteristics of Mature Dendritic Cells in Mice

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