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- 2016
vIL-10对鼻咽癌细胞株MHC-1类分子抗原加工提呈“操纵子”表达的影响
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Abstract:
摘要：目的 研究病毒白介素-10(vIL-10)对鼻咽癌细胞株MHC-1类分子抗原加工提呈“操纵子”表达的影响。方法 收集不同时间段vIL-10处理的鼻咽癌细胞(CNE-1和CNE-2)，采用RT-PCR、Western blot方法检测vIL-10处理的鼻咽癌细胞中MHC-1类分子抗原加工提呈“操纵子”(TAP-1、2，LMP-2、7及HLA-I)表达的变化。结果 ①mRNA水平：CNE-1和CNE-2的TAP-1水平在不同时间点均未表现出显著差异；vIL-10作用1、4、6、12h时，CNE-1和CNE-2的TAP-2、LMP-2均未出现变化，24h时，两者均出现显著下降甚至消失；CNE-1在vIL-10作用后4h即出现LMP-7下降，而CNE-2在vIL-10作用后6h出现下降；在vIL-10作用24h时CNE-1和CNE-2的HLA-I出现显著下降。②蛋白水平：vIL-10作用后24h时，两种细胞的TAP-1均出现显著下降，TAP-2则在vIL-10作用后1、6、12、24h出现逐渐下降；CNE-2的LMP-2、LMP-7在vIL-10作用后随时间逐渐下降，而CNE-1的两种蛋白仅在作用后12h出现显著下降；HLA-I在vIL-10作用后出现下降趋势，但在CNE-1中各时间段变化无统计学差异，CNE-2在24h显著下降。结论 vIL-10可明显抑制鼻咽癌MHC-I类分子抗原加工和提呈的“操纵子”的表达，并且呈一定的时间依赖性。
ABSTRACT: Objective To explore the effects of virus interleukin-10(vIL-10) on different expressions of MHC-I antigen processing "the operon". Methods We collected nasopharyngeal carcinoma cells (CNE-1 and CNE-2) treated by vIL-10 at different time points, and detected the changes of MHC-I antigen processing “the operons” (TAP-1, TAP-2，LMP-2, LMP-7 and HLA-I) by RT-PCR and Western blot. Results ① mRNA level: There was no difference in the expression of TAP-1 in CNE-1 and CNE-2 cells at various time points. The expressions of TAP-2 and LMP-2 in CNE-1 and CNE-2 did not change at 1, 4, 6, 12h, but downregulated and even disappeared at 24h. The expression of LMP-7 in CNE-1 decreased 4h after vIL-10 was added, and that in CNE-2 decreased at 6h. The expression of HLA-I in CNE-1 and CNE-2 showed significant decrease at 24h. ② Protein expression: The expression of TAP-1 in CNE-1 and CNE-2 showed significant decrease at 24h. The expression of TAP-2 in CNE-1 and CNE-2 was gradually downregulated at different time points. The expressions of LMP-2 and LMP-7 in CNE-2 were gradually downregulated at different periods, while that in CNE-1 was only decreased at 12h. The expression of HLA-I in CNE-1 and CNE-2 was gradually downregulated, but there was no significant difference at each period in CNE-1, while the expression of HLA-I in CNE-2 at 24h was significantly downregulated. Conclusion vIL-10 can inhibit the expression of MHC-I antigen processing "the operon" in NPC in the time-dependent manner
| [1] | LI W, DENG XM, WANG CX, et al. Down-regulation of HLA class I antigen in human papillomavirus type 16 E7 expressing HaCaT cells: correlate with TAP-1 expression[J]. Int J Gynecol Cancer, 2010, 20(2):227-232. |
| [2] | L？PEZ-ALBAITERO A, NAYAK JV, OGINO T, et al. Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL[J]. J Immunol, 2006, 176(6):3402-3409. |
| [3] | SETTE A, CHESNUT R, FIKES J. HLA expression in cancer: implications for T cell-based immunotherapy[J]. Immunogenetics, 2001, 53(4):255-263. |
| [4] | SINGAL DP, YE M, BIENZLE D. Transfection of TAP 1 gene restores HLA class I expression in human small-cell lung carcinoma[J]. Int J Cancer, 1998, 75(1):112-116. |
| [5] | WANG X, NI J, HSU CL, et al. Reduced expression of tocopherol-associated protein (TAP/Sec14L2) in human breast cancer[J]. Cancer Invest, 2009, 27(10):971-977. |
| [6] | FACOETTI A, Nano R, Zelini P, et al. Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors[J]. Clin Cancer Res, 2005, 11(23):8304-8311. |
| [7] | ZEIDLER R, EISSNER G, MEISSNER P, et al. Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10[J]. Blood, 1997, 90(6):2390-2397. |
| [8] | SCHOTTELIUS AJ, MAYO MW, SARTOR RB, et al. Interleukin-10 signaling blocks inhibitor of κB kinase activity and nuclear factor κB DNA binding[J]. J Biol Chem,1999, 274(45):31868-31874. |
| [9] | REN YX, YANG J, ZHANG LJ, et al. Downregulation of expression of transporters associated with antigen processing 1 and 2 and human leukocyte antigen I and its effect on immunity in nasopharyngeal carcinoma patients[J]. Mol Clin Oncol, 2014, 2(1):51-58. |
| [10] | RENNER C, TR？aMPER L, PFREUNDSCHUH M, et al. Tumour vaccines: a new immunotherapeutic approach in oncology[J]. Ann Hematol, 2000, 79(12):651-659. |
| [11] | SELIGER B. Different regulation of MHC class I antigen processing components in human tumors[J]. J Immunotoxicol, 2008, 5(4):361-367. |
| [12] | YANG T, MCNALLY BA, FERRONE S, et al. A single-nucleotide deletion leads to rapid degradation of TAP-1 mRNA in a melanoma cell line[J]. J Biol Chem, 2003, 278(17):15291-15296. |
| [13] | M？aLLER M, AGAIMY A, ZENK J, et al. The prognostic impact of human leukocyte antigen (HLA) class I antigen abnormalities in salivary gland cancer. A clinicopathological study of 288 cases[J]. Histopathology, 2013, 62(6):847-859. |
| [14] | SELIGER B. Molecular mechanisms of MHC class I abnormalities and APM components in human tumors[J]. Cancer Immunol Immunother, 2008, 57(11):1719-1726. |
| [15] | MEISSNER M, REICHERT TE, KUNKEL M, et al. Defects in the human leukocyte antigen class I antigen processing machinery in head and neck squamous cell carcinoma: association with clinical outcome[J]. Clin Cancer Res, 2005, 11(7):2552-2560. |
| [16] | RODR？PGUEZ JA, GALEANO L, PALACIOS DM, et al. Altered HLA class I and HLA-G expression is associated with IL-10 expression in patients with cervical cancer[J]. Pathobiology, 2012, 79(2):72-83. |
| [17] | YUE FY, DUMMER R, GEERTSEN R, et al. Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules[J]. Int J Cancer, 1997, 71(4):630-637. |
| [18] | 任艳鑫，李晓江，喻博，等. VIL-10下调鼻咽癌细胞TAP-1基因表达的研究[J]. 中国耳鼻咽喉头颈外科，2012, 19(5):255-257. |
| [19] | 任艳鑫，李晓江，杨洁，等. 鼻咽癌组织中BCRF-1基因表达及其与免疫功能的相关性分析[J]. 西安交通大学学报(医学版), 2012, 33(4):494-497. |
| [20] | EISENBACH L, BAR-HAIM E, EL-SHAMI K, et al. Antitumor vaccination using peptide based vaccines[J]. Immunol Lett, 2000, 74(1):27-34. |
| [21] | LEWIS JD, REILLY BD, BRIGHT RK, et al. Tumor-associated antigens: from discovery to immunity[J]. Int Rev Immunol, 2003, 22(2):81-112. |
