程序性死亡因子-1及其配体-1在子宫腺肌病中的表达及意义

doi:10.6040/j.issn.1671-7554.0.2017.157

摘要/Abstract

摘要： 目的探讨子宫腺肌病中程序性死亡因子-1(PD-1)及其配体-1(PD-L1)的表达,以及PD-1/PD-L1信号通路在子宫腺肌病发生发展中的作用。方法采用免疫组织化学法及Western blotting检测不同月经周期的子宫腺肌病在位内膜与异位子宫内膜、正常子宫内膜组织标本中PD-1、PD-L1蛋白的表达(每组增生期:n=15、分泌期:n=15)。分析不同组别间PD-1、PD-L1蛋白的表达差异及其与月经周期的关系。结果免疫组织化学结果显示,PD-1、PD-L1在不同月经周期的正常子宫内膜及腺肌病在位、异位子宫内膜中均有表达。腺肌病异位子宫内膜中PD-1蛋白(P<0.01)与PD-L1蛋白(P<0.01)表达升高。Western blotting结果显示,腺肌病在位子宫内膜中PD-1蛋白(P<0.01)与PD-L1蛋白(P<0.01)的表达增高。但在腺肌病组内不同月经周期中,PD-1/PD-L1的表达水平差异无统计学意义(P=0.12; P=0.45)。结论 PD-1蛋白及PD-L1蛋白在腺肌病在位及异位子宫内膜中的表达升高,提示PD-1/PD-L1信号通路可能参与子宫腺肌病的发生、发展过程。

关键词: 子宫腺肌病, 程序性死亡因子-1, 免疫耐受, 程序性死亡因子配体-1, 子宫内膜

Abstract: Objective To investigate the expression and significance of PD-1 and its ligand PD-L1 in adenomyosis. Methods The expression level of PD-1 and PD-L1 in normal endometria, eutopic and ectopic adenomyotic endometria were determined by immunohistochemistry and Western blotting(proliferative phase n=15; secretory phase n=15 in each group). In addition, the relationship between different expressions of PD-1/PD-L1 among groups and menstrual cycle was analyzed. Results PD-1/PD-L1 expressed in both normal and adenomyotic endometria of different menstrual cycles. In addition, expressions of PD-1/PD-L1 in both ectopic and eutopic adenomyotic endometria were upregulated(P<0.01). However, there was no difference between proliferative phase and secretory phase in PD-1/PD-L1 expression of eutopic adenomyotic endometria(P=0.12; P=0.45). Conclusion The expressions of PD-1 and PD-L1 are upregulated in adenomyotic endometria, suggesting that the PD-1/PD-L1 pathway may be involved in the immune dysfunctions and pathogenesis of adenomyosis.

Key words: Adenomyosis, Programmed cell death-ligand 1, Immunotolerance, Programmed death-1, Endometrium

中图分类号:

R711.71

吴卢侃璇,朱珊,于金习,吕椿子,李明江. 程序性死亡因子-1及其配体-1在子宫腺肌病中的表达及意义[J]. 山东大学学报（医学版）, 2017, 55(10): 90-96.

WU Lukanxuan, ZHU Shan, YU Jinxi, LÜ Chunzi, LI Mingjiang. Expression and significance of programmed death-1 and its ligand PD-L1 in adenomyosis[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(10): 90-96.

参考文献

[1] 郎景和. 关于子宫内膜异位症的再认识及其意义[J]. 中国工程科学, 2009:137-142.
[2] Tremellen KP, Russell P. The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. Ii: Adenomyosis and macrophages[J]. J Reprod Immunol, 2012, 93(1): 58-63.
[3] Wang F, Wen Z, Li H, et al. Human leukocyte antigen-g is expressed by the eutopic and ectopic endometrium of adenomyosis[J]. Fertil Steril, 2008, 90(5): 1599-1604.
[4] Yu JJ, Sun HT, Zhang ZF, et al. Il15 promotes growth and invasion of endometrial stromal cells and inhibits killing activity of nk cells in endometriosis[J]. Reproduction, 2016, 152(2): 151-160.
[5] O DF, Roskams T, Van den Eynde K, et al. The presence of endometrial cells in peritoneal fluid of women with and without endometriosis[J]. Reprod Sci, 2017, 24(2): 242-251.
[6] Okazaki T, Honjo T. The pd-1-pd-l pathway in immunological tolerance[J]. Trends Immunol, 2006, 27(4): 195-201.
[7] Francisco LM, Sage PT, Sharpe AH. The pd-1 pathway in tolerance and autoimmunity[J]. Immunol Rev, 2010, 236: 219-242. doi: 10.1111/j.1600-065X.2010.00923.x.
[8] Chikuma S. Basics of pd-1 in self-tolerance, infection, and cancer immunity[J]. Int J Clin Oncol, 2016, 21(3): 448-455.
[9] Sotnikova N, Antsiferova I, Malyshkina A. Cytokine network of eutopic and ectopic endometrium in women with adenomyosis[J]. Am J Reprod Immunol, 2002, 47(4): 251-255.
[10] 张爱荣, 吴继海, 胡本忠, 等. 子宫内膜异位症并不孕患者腹腔液及外周血中细胞因子的变化[J]. 山东大学学报(医学版), 2004, 42(4): 460-462. ZHANG Airong, WU Jihai, HU Benzhong, et al. Interleukin variation in peritoneal fluid and serum of patients with endometriosis-related infertility[J]. Journal of Shandong University(Health Sciences), 2004, 42(4): 460-462.
[11] 王立杰, 冷金花, 郎景和. IL-8在子宫内膜异位症发病中的作用[J]. 山东大学学报(医学版), 2004, 42(4): 456-459. WANG Lijie, LENG Jinhua, LANG Jinghe. Role of interleukine-8 in the pathogenesis of endometriosis[J]. Journal of Shandong University(Health Sciences), 2004, 42(4): 456-459.
[12] Nishimura H, Honjo T. Pd-1: An inhibitory immunoreceptor involved in peripheral tolerance[J]. Trends Immunol, 2001, 22(5): 265-268.
[13] Keir ME, Butte MJ, Freeman GJ, et al. Pd-1 and its ligands in tolerance and immunity[J]. Annu Rev Immunol, 2008, 26: 677-704. doi: 10.1146/annurev.immunol.26.021607.090331.
[14] Latchman Y, Wood CR, Chernova T, et al. Pd-l2 is a second ligand for pd-1 and inhibits t cell activation[J]. Nat Immunol, 2001, 2(3): 261-268.
[15] Scheerer C, Bauer P, Chiantera V, et al. Characterization of endometriosis-associated immune cell infiltrates(emaici)[J]. Arch Gynecol Obstet, 2016, 294(3): 657-664.
[16] Dong H, Strome SE, Salomao DR, et al. Tumor-associated b7-h1 promotes t-cell apoptosis: a potential mechanism of immune evasion[J]. Nat Med, 2002, 8(8): 793-800.
[17] Mazanet MM, Hughes CC. B7-h1 is expressed by human endothelial cells and suppresses t cell cytokine synthesis[J]. J Immunol, 2002, 169(7): 3581-3588.
[18] Kim S, Koh J, Kim MY, et al. Pd-l1 expression is associated with epithelial-to-mesenchymal transition in adenocarcinoma of the lung[J]. Hum Pathol, 2016, 58: 7-14. doi:10.1016/j.humpath.2016.07.007.
[19] Webb JR, Milne K, Kroeger DR, et al. Pd-l1 expression is associated with tumor-infiltrating t cells and favorable prognosis in high-grade serous ovarian cancer[J]. Gynecol Oncol, 2016, 141(2): 293-302.
[20] Madore J, Strbenac D, Vilain R, et al. Pd-l1 negative status is associated with lower mutation burden, differential expression of immune-related genes, and worse survival in stage-iii melanoma[J]. Clin Cancer Res, 2016, 22(15): 3915-3923.
[21] Madore J, Vilain RE, Menzies AM, et al. Pd-l1 expression in melanoma shows marked heterogeneity within and between patients: Implications for anti-pd-1/pd-l1 clinical trials[J]. Pigment Cell Melanoma Res, 2015, 28(3): 245-253.
[22] Merelli B, Massi D, Cattaneo L, et al. Targeting the pd1/pd-l1 axis in melanoma: biological rationale, clinical challenges and opportunities[J]. Crit Rev Oncol Hematol, 2014, 89(1): 140-165.
[23] Chang K, Svabek C, Vazquez-Guillamet C, et al. Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses t cell exhaustion in patients with sepsis[J]. Crit Care, 2014, 18(1): R3. doi: 10.1186/cc13176.
[24] Yang L, Huang F, Mei J, et al. Posttranscriptional control of pd-l1 expression by 17beta-estradiol via pi3k/akt signaling pathway in eralpha-positive cancer cell lines[J]. Int J Gynecol Cancer, 2017, 27(2): 196-205.

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