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| Effect of Total Glucosides of Paeony on the Expression of Natural Killer T Cells in Livers of Experimental Autoimmune Uveitis Rats |
| Changying Jing1,2, Jike Song1,2, Beibei Wang1,3, QingMei Tian1,3, Xiaofeng Xie1,3, Tao Zhang2, Hongsheng Bi1,4 |
1Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Jinan 250002, China;
2Shandong University of Traditional Chinese Medicine, Jinan 250014, China;
3Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250002, China;
4Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan 250002, China |
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Abstract Objective:To investigate the effects of total glucosides of paeony (TGP) on natural killer T (NKT) cell gene expression in liver of experimental autoimmune uveitis (EAU) rats. Methods:Experimental study. Forty-five Lewis rats were randomly divided into three groups: normal controls, EAU-stimulated rats (model group), and EAU-stimulated rats treated with TGP (TGP intervention group). Control animals received an emulsion of phosphate-buffered saline (PBS) and CFA, which was injected subcutaneously. The other two groups were injected an equal volume of chylomicron containing interphotoreceptor retinoid-binding protein polypeptide (IRBP). Inflammation was observed by daily slit-lamp microscopy of the anterior segments after immunization. The incidence of inflammation and the inflammation scores were recorded. At 12 days after immunization, we extracted the eyes for pathologic examination, and CD4+ T cells were collected from the livers. The expression levels of NKT cells were detected by flow cytometry. Reverse transcription polymerase change reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to measure the gene and protein expression levels of interleukin (IL)-4 and interferon (IFN)-γ. Data were analyzed by one-way ANOVA. Results:Twelve days after immunization, the inflammatory score and pathological grade of the TGP group were significantly lower than in the EAU group, but higher than in the normal group. Flow cytometry showed that compared with normal control group, the number of liver NKT cells in the EAU group and in the TGP intervention group were significantly increased. Further, the increased in the number of NKT expression in the TGP intervention group was higher than in the EAU group (P<0.05) during the inflammatory phase. RT-PCR showed that on day 12 the expression of IFN-γ mRNA in the liver of the TGP intervention group was significantly higher than in the control group (P<0.001), but lower than in the EAU group (P<0.001). At the same time, the expression of liver IL-4 mRNA in the TGP group was lower than that of the normal group (P<0.001), but significantly higher than the EAU group (P<0.001). ELISA showed that the liver IFN-γ levels in the TGP group were significantly lower in the EAU group after 12 days (P=0.01). The concentration of liver IL-4 protein was higher in the TGP group than in the EAU group (P<0.001). Conclusions:TGP can treat uveitis in EAU rats by regulating the expression of liver IL-4 and IFN-γ genes and increasing the number of NKT cells.
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Received: 07 April 2018
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| Fund:National Natural Science Foundation of China (81674032); Key Research and Development Project of Shandong Province (2016GSF202031) |
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Corresponding Authors:
Hongsheng Bi, Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan 250002, China (Email: hongshengbi1@163.com)
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| [1] |
何唯, 侯琦, 黄旭东, 等. 白藜芦醇对内毒素诱导的大鼠葡萄膜炎的治疗作用. 中华眼视光学与视觉科学杂志, 2017, 19(8): 488-495. DOI: 10.3760/cma.j.issn.1674-845X.2017.08. 007.
|
| [2] |
杨培增, 张震. 葡萄膜炎免疫治疗的进展与展望. 中华眼科杂志, 2002, 38(9): 574-576. DOI: 10.3760/j:issn:0412-4081. 2002.09.022.
|
| [3] |
毕宏生, 解孝锋, 吴建峰. 中医药综合治疗葡萄膜炎临床评价分析. 国际眼科杂志, 2009, 9(4): 749-751. DOI: 10.3969/j.issn. 1672-5123.2009.04.044.
|
| [4] |
王希民, 刘维. 白芍总苷联合维生素D3对类风湿关节炎患者血清中IFN-γ和IL-10的影响. 中国中医药信息杂志, 2008, (7): 15-17. DOI: 10.3969/j.issn.1005-5304.2008.07.008.
|
| [5] |
Racanelli V, Rehermann B.The liver as an immunological organ. Hepatology, 2006, 43(Suppl 1): S54-S62.
|
| [6] |
Lin W, Man X, Li P, et al.NK cells are negatively regulated by sCD83 in experimental autoimmune uveitis. Sci Rep, 2017, 7(1): 12895. DOI: 10.1038/s41598-017-13412-1.
|
| [7] |
Santodomingo-Garzon T, Swain MG.Role of NKT cells in autoimmune liver disease. Autoimmun Rev, 2011, 10(12): 793-800. DOI: 10.1016/j.autrev.2011.06.003.
|
| [8] |
Kumar V.NKT-cell subsets: promoters and protectors in inflammatory liver disease. J Hepatol, 2013, 59(3): 618-620. DOI: 10.1016/j.jhep.2013.02.032.
|
| [9] |
Gianchecchi E, Delfino DV, Fierabracci A.NK cells in autoimmune diseases: Linking innate and adaptive immune responses. Autoimmun Rev, 2018, 17(2): 142-154. DOI: 10.1016/j.autrev.2017.11.018.
|
| [10] |
李志军, 梅永君, 陈琳洁, 等. 白芍总苷治疗未分化脊柱关节病疗效及其机制探讨. 中国中医药信息杂志, 2010, 17(1): 14-16. DOI: 10.3969/j.issn.1005-5304.2010.01.007.
|
| [11] |
杨培增, 杜利平. 我国葡萄膜炎基础研究的现状. 中华眼视光学与视觉科学杂志, 2015, 17(5): 257-260. DOI: 10.3760/cma.j.issn.1674-845X.2015.05.001.
|
| [12] |
Miko E, Meggyes M, Doba K, et al.Characteristics of peripheral blood NK and NKT-like cells in euthyroid and subclinical hypothyroid women with thyroid autoimmunity experiencing reproductive failure. J Reprod Immunol, 2017, 124: 62-70. DOI: 10.1016/j.jri.2017.09.008.
|
| [13] |
Tian Z, Gershwin ME, Zhang C.Regulatory NK cells in autoimmune disease. J Autoimmun, 2012, 39(3): 206-215. DOI: 10.1016/j.jaut.2012.05.006.
|
| [14] |
Martín-Fontecha A, Thomsen LL, Brett S, et al.Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat Immunol, 2004, 5(12): 1260-1265. DOI: 10.1038/ni1138.
|
| [15] |
邵家胜. TB患者NKT细胞数量与功能的研究及α-GalCer对Mtb感染后小鼠体内NKT细胞功能的影响. 上海: 复旦大学, 2013.
|
| [16] |
Cerwenka A, Pahl J.NK Cells in Antitumor Immunity. Encyclop Immun, 2016: 487-492. DOI: 10.1016/13978-0-12-374279-7.
|
| [17] |
Grajewski RS, Hansen AM, Agarwal RK, et al.Activation of invariant NKT cells ameliorates experimental ocular autoimmunity by a mechanism involving innate IFN-gamma production and dampening of the adaptive Th1 and Th17 responses. J Immunol, 2008, 181(7): 4791-4797.
|
| [18] |
Mars LT, Araujo L, Kerschen P, et al.Invariant NKT cells inhibit development of the Th17 lineage. Proc Natl Acad Sci USA, 2009, 106(15): 6238-6243. DOI: 10.1073/pnas.0809317106.
|
| [19] |
Oh K, Byoun OJ, Ham DI, et al.Invariant NKT cells regulate experimental autoimmune uveitis through inhibition of Th17 differentiation. Eur J Immunol, 2011, 41(2): 392-402. DOI: 10.1002/eji.201040569.
|
| [20] |
Satoh M, Namba KI, Kitaichi N, et al.Invariant natural killer T cells play dual roles in the development of experimental autoimmune uveoretinitis. Exp Eye Res, 2016, 153: 79-89. DOI: 10.1016/j.exer.2016.10.003.
|
| [21] |
Lacomba MS, Martin CM, Chamond RR, et al.Aqueous and serum interferon gamma, interleukin (IL) 2, IL-4, and IL-10 in patients with uveitis. Arch Ophthalmol, 2000, 118(6): 768-772.
|
|
|
|
2018, Vol. 20 
