JNK通路对M2巨噬细胞极化及其肿瘤效应的影响

doi:10.13523/j.cb.20180401

中国生物工程杂志

2018, Vol. 38

Issue (4): 1-7 DOI: 10.13523/j.cb.20180401

研究报告

JNK通路对M2巨噬细胞极化及其肿瘤效应的影响

郝瑾¹,朱子鑫²,吕小岩³,周钦^1*

1 重庆医科大学检验医学院临床检验诊断学教育部重点试验室重庆 400016
2 重庆市第八中学重庆 400016
3 华西医院皮肤科成都 610000

Effects of JNK Pathway on Polarization and Pro-tumor Function of M2 Macrophage

Jin HAO¹,Zi-xin ZHU²,Xiao-yan LV³,Qin ZHOU^1*

1 Key Laboratory of Laboratory Medical Diagnostics of Education Ministry,College of Laboratory Medicine, Chongqing Medical University,Chongqing 400016,China
2 Chongqing No.8 Secondary School,Chongqing 400016, China
3 Department of Dermatology, West China Hospital, Chengdu 610000, China

全文: PDF(1266 KB) HTML

摘要：

探究了JNK通路对M2巨噬细胞极化及M2介导的促肿瘤效应的影响。构建单核细胞THP1来源M2 巨噬细胞模型(THP1-M2),将细胞分为3组: 用PMA 诱导的未活化巨噬细胞组(M0),用PMA、IL-4处理及阴性干扰(DMSO)的M2型巨噬细胞组(M2),用特异性抑制剂阻断JNK通路的M2 型巨噬细胞组(M2-JNKI)。实时荧光定量PCR检测M2 表型marker基因的表达;免疫蛋白印迹法检测M2 表型marker蛋白水平;细胞划痕试验检测巨噬细胞迁移能力;流式细胞数检测786O及OSRC2凋亡。结果与THP1-M2组相比,阻断JNK通路的M2组M2表型marker表达明显下降,同时其细胞迁移能力也呈下降趋势。且阻断JNK通路后,M2巨噬细胞抑制肾癌细胞凋亡的能力减弱。结果表明,抑制JNK通路后,M2巨噬细胞极化状态受损,其促肿瘤效应可转变为抗肿瘤效应。

关键词： JNK通路; M2极化; 肿瘤; IL-4

Abstract:

The present study investigates the effect of JNK pathway on the polarization of M2 status as well as pro-tumor function mediated by M2. THP1 derived M2 macrophage (THP1-M2) model was established. The cells were divided into 3 groups: the PMA pretreated unpolarized macrophage (M0), the PMA and IL-4 induced M2 macrophage with DMSO (negative control) treated (M2), the JNK inhibitor treated M2 macrophage (M2-JNK I). Furthermore, the M2 associated markers Arginase1 (Arg1),mannose receptor C-type 1 (Mrc1)were analyzed by Q-PCR, the protein level of Arg1 and Mrc1 were detected by Western blot, the migration ability of macrophages was tested by Wound Healing, the apoptosis of 786O and OSRC2 were analyzed by flow cytometry. Compared with the THP1-M2, THP1-M2-JNK I group showed decreased expression of Arg1 and Mrc1, and migration ability was impaired. What’s more, block of JNK pathway inhibited the pro-tumor function of M2 on 786O and OSCR2. Taken together, the results suggest that inhibition of JNK pathway regulates M2 polarization and its pro-tumor effects.

Key words: JNK pathway M2 polarization Tumor IL-4

收稿日期: 2017-10-19 出版日期: 2018-05-08

ZTFLH:

Q257

基金资助: * 国家自然科学基金(31401191)

	服务
	把本文推荐给朋友
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	郝瑾
	朱子鑫
	吕小岩
	周钦

引用本文:

郝瑾,朱子鑫,吕小岩,周钦. JNK通路对M2巨噬细胞极化及其肿瘤效应的影响[J]. 中国生物工程杂志, 2018, 38(4): 1-7.

Jin HAO,Zi-xin ZHU,Xiao-yan LV,Qin ZHOU. Effects of JNK Pathway on Polarization and Pro-tumor Function of M2 Macrophage. China Biotechnology, 2018, 38(4): 1-7.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20180401 或 https://manu60.magtech.com.cn/biotech/CN/Y2018/V38/I4/1

表1 引物列表

图1 THP1-M2 巨噬细胞表面标志物表达情况

图2 JNK I对THP1-M2 巨噬细胞极化状态的影响

图3 JNK I对THP1-M2 巨噬细胞极化状态的影响

图4 流式细胞术检测不同条件培养基对肾癌细胞凋亡的影响

[1]	Sica A, Mantovani A . Macrophage plasticity and polarization: in vivo veritas. Journal of Clinical Investigation, 2006,108(2):408-409.
[2]	Chinetti-Gbaguidi G, Colin S, Staels B . Macrophage subsets in atherosclerosis. Nature Reviews Cardiology, 2015,12(1):10. doi: 10.1038/nrcardio.2014.173
[3]	Wynn T A, Chawla A, Pollard J W . Macrophage biology in development, homeostasis and disease. Nature, 2013,496(7446):445-455. doi: 10.1038/nature12034 pmid: 23619691
[4]	Zheng X F, Hong Y X, Feng G J , et al. Lipopolysaccharide-induced M2 to M1 macrophage transformation for IL-12p70 production is blocked by Candida albicans mediated up-regulation of EBI3 expression. PLoS One, 2013,8(5):e63967. doi: 10.1371/journal.pone.0063967 pmid: 3664618
[5]	Martinez F O, Helming L, Gordon S . Alternative activation of macrophages: an immunologic functional perspective. Annual Review of Immunology, 2009,27(1):451-483. doi: 10.1146/annurev.immunol.021908.132532 pmid: 19105661
[6]	Murray P J, Wynn T A . Protective and pathogenic functions of macrophage subsets. Nature Reviews Immunology, 2011,11(11):723-737. doi: 10.1038/nri3073 pmid: 21997792
[7]	Moreno J L, Kaczmarek M, Keegan A D , et al. IL-4 suppresses osteoclast development and mature osteoclast function by a STAT6-dependent mechanism: irreversible inhibition of the differentiation program activated by RANKL. Blood, 2003,102(3):1078-1086. doi: 10.1182/blood-2002-11-3437 pmid: 12689929
[8]	Jiang H, Harris M B, Rothman P . IL-4/IL-13 signaling beyond JAK/STAT. Journal of Allergy and Clinical Immunology, 2000,105(6):1063-1070. doi: 10.1067/mai.2000.107604
[9]	Hao J, Hu Y, Li Y , et al. Involvement of JNK signaling in IL-4 induced M2 macrophage polarization. Experimental Cell Research, 2017,357(2):155-162. doi: 10.1016/j.yexcr.2017.05.010 pmid: 28501460
[10]	Zhou Y, Zhang T, Wang X , et al. Curcumin modulates macrophage polarization through the inhibition of the toll-like receptor 4 expression and its signaling pathways. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 2015,36(2):631-641.
[11]	Martinez F O, Helming L, Milde R , et al. Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences. Blood, 2013,121(9):e57-69. doi: 10.1182/blood-2012-06-436212 pmid: 23293084
[12]	Zou J, Shankar N . Roles of TLR/MyD88/MAPK/NF-kappaB signaling pathways in the regulation of phagocytosis and proinflammatory cytokine expression in response to E. faecalis infection. PLoS One, 2015,10(8):e0136947. doi: 10.1371/journal.pone.0136947 pmid: 4552673
[13]	Xiong C Y, Guan D W, Liu Z H , et al. Changes of phospho-JNK expression during the skin burned wound healing. Journal of Forensic Medicine, 2008,24(5):325-335. pmid: 18979912
[14]	Gnanaprakasam J N, Estrada-Muniz E, Vega L . The anacardic 6-pentadecyl salicylic acid induces macrophage activation via the phosphorylation of ERK1/2, JNK, P38 kinases and NF-kappaB. International Immunopharmacology, 2015,29(2):808-817. doi: 10.1016/j.intimp.2015.08.038 pmid: 26371858
[15]	Sica A, Bronte V . Altered macrophage differentiation and immune dysfunction in tumor development. Journal of Clinical Investigation, 2007,117(5):1155-1166. doi: 10.1172/JCI31422 pmid: 17476345
[16]	Nakanishi Y, Nakatsuji M, Seno H , et al. COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to M1 in ApcMin/+ mouse polyps. Carcinogenesis, 2011,32(9):1333-1339. doi: 10.1093/carcin/bgr128 pmid: 21730361
[17]	Swartz M A, Iida N, Roberts E W , et al. Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Research, 2012,72(10):2473. doi: 10.1158/0008-5472.CAN-12-0122 pmid: 22414581
[18]	Smit-Peter S Y . The role of cytokine in regulation of the natural killer cell activity. Srp Arh Celok Lek, 2008,136(7):423-429. doi: 10.2298/SARH0808423J pmid: 18959181
[19]	Engel M A, Neurath M F . Anticancer properties of the IL-12 family--focus on colorectal cancer. Current Medicinal Chemistry, 2010,17(29):3303. doi: 10.2174/092986710793176366 pmid: 20712574
[20]	Hanlon A M, Jang S, Salgame P . Signaling from cytokine receptors that affect Th1 responses. Frontiers in Bioscience A Journal & Virtual Library, 2002,7(7):d1247. doi: 10.2741/hanlon pmid: 11991837

[1]	赵梦泽,李凤智,王鹏银,李剑,徐寒梅. PD-L1和VEGF双靶点联合阻断治疗的研究进展[J]. 中国生物工程杂志, 2021, 41(9): 71-77.
[2]	吕慧中,赵晨辰,朱链,许娜. 外泌体靶向递药在肿瘤治疗中的进展[J]. 中国生物工程杂志, 2021, 41(5): 79-86.
[3]	原博,王杰文,康广博,黄鹤. 双特异性纳米抗体的研究进展及其应用 ^*[J]. 中国生物工程杂志, 2021, 41(2/3): 78-88.
[4]	邓蕊,曾佳利,卢雪梅. 基于Musca domestica cecropin的抗肿瘤小分子衍生肽筛选及构效关系解析^*[J]. 中国生物工程杂志, 2021, 41(11): 14-22.
[5]	蔺士新,刘东晨,雷云,熊盛,谢秋玲. TNF-α纳米抗体的筛选、表达及特异性检测 ^*[J]. 中国生物工程杂志, 2020, 40(7): 15-21.
[6]	杨威,宋方祥,王帅,张黎,王红霞,李焱. 药物输送系统中Janus纳米粒子的制备及应用 ^*[J]. 中国生物工程杂志, 2020, 40(7): 70-81.
[7]	张保惠,熊华龙,张天英,袁权. 基于水疱性口炎病毒(VSV)的溶瘤病毒研究进展 ^*[J]. 中国生物工程杂志, 2020, 40(6): 53-62.
[8]	童梅,程永庆,刘金毅,徐晨. 促进大肠杆菌周质空间小分子抗体表达的菌种构建方法^*[J]. 中国生物工程杂志, 2020, 40(5): 48-56.
[9]	戴奇男,张景红. 肿瘤多药耐药与自噬、DNA修复和肿瘤干细胞相关的分子机制研究进展 ^*[J]. 中国生物工程杂志, 2020, 40(4): 69-77.
[10]	钱颖,钱晨,白晓庆,王晶晶. 免疫佐剂在肿瘤免疫疗法中的应用进展 ^*[J]. 中国生物工程杂志, 2020, 40(3): 96-103.
[11]	肖雪筠,唐奇,新华·那比. 靶向肿瘤微环境的CAR-T治疗研究^*[J]. 中国生物工程杂志, 2020, 40(12): 67-74.
[12]	何询,张鹏,张俊祥. 类器官的构建与应用进展[J]. 中国生物工程杂志, 2020, 40(12): 82-87.
[13]	朱永朝,陶金,任萌萌,熊燃,何亚琴,周瑜,卢震辉,杜勇,杨芝红. 自噬抑制肿瘤坏死因子α诱导人胎盘胎儿来源间充质干细胞发生凋亡 ^*[J]. 中国生物工程杂志, 2019, 39(9): 62-67.
[14]	彭贤贵,杨武晨,李佳,苟阳,王平,刘思恒,张云,李艺,张曦. 细胞形态相关技术在血液系统肿瘤中的应用 ^*[J]. 中国生物工程杂志, 2019, 39(9): 84-90.
[15]	刘艳,戴鹏,朱运峰. 外泌体作为肿瘤标志物的研究进展 ^*[J]. 中国生物工程杂志, 2019, 39(8): 74-79.

Viewed

Full text

Abstract

Cited

Shared

Discussed