胰岛素样生长因子1-磷脂酰肌醇3激酶/哺乳动物雷帕霉素靶蛋白通路对T细胞与角质形成细胞共培养模型中炎性细胞因子的影响

doi:10.13701/j.cnki.kqyxyj.2019.04.022

口腔医学研究 ›› 2019, Vol. 35 ›› Issue (4): 397-400.DOI: 10.13701/j.cnki.kqyxyj.2019.04.022

胰岛素样生长因子1-磷脂酰肌醇3激酶/哺乳动物雷帕霉素靶蛋白通路对T细胞与角质形成细胞共培养模型中炎性细胞因子的影响

马瑞洁, 谭雅芹, 周刚^*

武汉大学口腔医学院口腔生物医学工程教育部重点实验室,武汉大学口腔医学院口腔黏膜科湖北武汉 430079)

收稿日期:2018-10-27 出版日期:2019-04-28 发布日期:2019-04-23
通讯作者: 周刚,E-mail:zhougang@whu.edu.cn
作者简介:马瑞洁(1992~ ),女,河北唐山人,硕士在读,主要从事口腔黏膜病学方向研究。
基金资助:
国家自然科学基金(编号:81771080、81371147)

IGF1-PI3K/mTOR Pathway Has Regulatory Effects on Cytokines in T cells and Keratinocytes Co-culture System

MA Rui-jie, TAN Ya-qin, ZHOU Gang^*

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University;Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China

Received:2018-10-27 Online:2019-04-28 Published:2019-04-23

摘要/Abstract

摘要： 目的: 检测在口腔扁平苔藓中异常活化的胰岛素样生长因子1-磷脂酰肌醇3激酶/哺乳动物雷帕霉素靶蛋白 (insulin-like growth factor 1-phosphatidylinositol-3-kinase/the mammalian target of rapamycin,IGF1-PI3K/mTOR)信号通路对T细胞与角质形成细胞共培养环境中炎性细胞因子的影响。方法: 通过外源性IGF1、LY294002、雷帕霉素评估IGF-PI3K/mTOR信号通路在活化T细胞中的作用,构建T细胞与角质形成细胞共培养模型,运用酶联免疫吸附试验 (enzyme-linked immunosorbnent assay,ELISA)法检测细胞培养上清中白细胞介素-2(interleukin-2,IL-2)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)分泌情况。结果: 与单独培养的T细胞比较,T细胞与角质形成细胞共培养能促进TNF-α的分泌(P<0.05),而对IL-2的分泌无明显影响;而IGF1-PI3K/mTOR通路可减少共培养环境中IL-2 和 TNF-α水平(P<0.05)。结论: IGF1-PI3K/mTOR信号通路可调控T细胞与角质形成细胞共培养模型中炎性细胞因子的分泌,可能参与了口腔扁平苔藓免疫炎症的发生发展。

关键词: 口腔扁平苔藓, T细胞, 角质形成细胞, 胰岛素样生长因子1-磷脂酰肌醇3激酶/哺乳动物雷帕霉素靶蛋白

Abstract: Objective: To investigate the influence of IGF1-PI3K/MTOR signaling pathway, which was abnormally activated in OLP, on the inflammatory cytokines in the interaction of T cells and keratinocytes in oral lichen planus (OLP). Methods: A transwell co-culture system composed of T cells and oral keratinocytes was used as a model of OLP in vitro. The effects of activated T cells pretreated with LY294002, rapamycin, and IGF1 on the levels of IL-2 and TNF-α in supernatant from T cell alone and co-culture system were detected via ELISA, respectively. Results: Compared to the T cells cultured alone, the interaction of keratinocytes and T cells could increase the secretion of TNF-α (P<0.05), but has no impact on the level of IL-2. Whereas the aberrant IGF1-PI3K/MTOR signaling decreased the IL-2 and TNF-α secretion in the co-culture system (P<0.05). Conclusion: The IGF1-PI3K/MTOR signaling may modulate the cytokine networks in the crosstalk between T cells and keratinocytes and participate in the progression of OLP.

Key words: Oral lichen planus, T cells, Keratinocytes, IGF-PI3K/MTOR pathway

马瑞洁, 谭雅芹, 周刚. 胰岛素样生长因子1-磷脂酰肌醇3激酶/哺乳动物雷帕霉素靶蛋白通路对T细胞与角质形成细胞共培养模型中炎性细胞因子的影响[J]. 口腔医学研究, 2019, 35(4): 397-400.

MA Rui-jie, TAN Ya-qin, ZHOU Gang. IGF1-PI3K/mTOR Pathway Has Regulatory Effects on Cytokines in T cells and Keratinocytes Co-culture System[J]. Journal of Oral Science Research, 2019, 35(4): 397-400.

参考文献

[1] 卢锐.口腔扁平苔藓的目标治疗:观点和展望[J].口腔医学研究,2016,32(11): 1213-1216.
[2] Gupta S, Jawanda MK. Oral lichen planus: an update on etiology, pathogenesis, clinical presentation, diagnosis and management [J]. Indian J Dermatol, 2015, 60(3): 222-229.
[3] Payeras MR, Cherubini K, Figueiredo MA, et al. Oral lichen planus: focus on etiopathogenesis [J]. Arch Oral Biol, 2013, 58(9): 1057-1069.
[4] Zhang J, Tan YQ, Wei MH, et al. TLR4-induced B7-H1 on keratinocytes negatively regulates CD4⁺ T cells and CD8⁺ T cells responses in oral lichen planus [J]. Exp Dermatol, 2017, 26(5): 409-415.
[5] Stark AK, Sriskantharajah S, Hessel EM, et al. PI3K inhibitors in inflammation, autoimmunity and cancer [J]. Curr Opin Pharmacol, 2015, 23: 82-91.
[6] Fruman D, Chiu H, Hopkins B, et al. The PI3K pathway in human disease [J]. Cell, 2017, 170(4): 605-635.
[7] Be Liu AN, Pistol G, Marica CM, et al. PI3K/Akt signaling in peripheral T lymphocytes from systemic lupus erythematosus patients [J]. Roum Arch Microbiol Immunol, 2009, 68(2): 69-79.
[8] Erasalo H, Laavola M, Hamalainen M, et al. PI3K inhibitors LY294002 and IC87114 reduce inflammation in carrageenan-induced paw oedema and down-regulate inflammatory gene expression in activated macrophages [J]. Basic Clin Pharmacol Toxicol, 2015, 116(1): 53-61.
[9] Liu Y, Zhang DT, Liu XG. mTOR signaling in T cell immunity and autoimmunity [J]. Int Rev Immunol, 2015, 34(1): 50-66.
[10] Smith TJ. Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases [J]. Pharmacol Rev, 2010, 62(2): 199-236.
[11] Guo J, Zheng D, Li WF, et al. Insulin-like growth factor 1 treatment of MSCs attenuates inflammation and cardiac dysfunction following MI [J]. Inflammation, 2014, 37(6): 2156-2163.
[12] Zhang N, Zhang J, Tan YQ, et al. Activated Akt/mTOR-autophagy in local T cells of oral lichen planus [J]. Int Immunopharmacol, 2017, 48:84-90.
[13] Tan YQ, Zhang J, Du GF, et al. Altered autophagy-associated genes expression in T cells of oral lichen planus correlated with clinical features [J]. Mediators Inflamm, 2016, 2016:4867368.
[14] Malek T, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity [J]. Immunity, 2010, 33(2): 153-165.
[15] Lu R, Zhang J, Sun W, et al. Inflammation-related cytokines in oral lichen planus: an overview [J]. J Oral Pathol Med, 2015, 44(1): 1-14.
[16] Humberto J, Pavanin J, Rocha M, et al. Cytokines, cortisol, and nitric oxide as salivary biomarkers in oral lichen planus: a systematic review [J]. Braz Oral Res, 2018, 32: e82.
[17] Alrashdan MS, Cirillo N, Mccullough M. Oral lichen planus: a literature review and update [J]. Arch Dermatol Res, 2016, 308(8): 539-551.
[18] Cao G, Wang Q, Li G, et al. mTOR inhibition potentiates cytotoxicity of Vgamma4 gammadelta T cells via up-regulating NKG2D and TNF-alpha [J]. J Leukoc Biol, 2016, 100(5): 1181-1189.

胰岛素样生长因子1-磷脂酰肌醇3激酶/哺乳动物雷帕霉素靶蛋白通路对T细胞与角质形成细胞共培养模型中炎性细胞因子的影响

IGF1-PI3K/mTOR Pathway Has Regulatory Effects on Cytokines in T cells and Keratinocytes Co-culture System

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	张黎, 刘育菘, 吴芸菲, 符起亚. 基于IL-23/Th17炎症轴探讨葛根素对大鼠牙周炎牙槽骨吸收及OPG/RANKL/RANK通路的影响[J]. 口腔医学研究, 2020, 36(9): 844-849.
[2]	孟文霞, 冯璐, 刘曙光, 周会喜, 李志强. 口腔扁平苔藓活化成纤维细胞对血管内皮细胞迁移及成管特性的影响[J]. 口腔医学研究, 2019, 35(8): 806-809.
[3]	王亚敏, 孟文霞, 周震, 郭薇, 谢宝仪. 口腔扁平苔藓组织中α-平滑肌肌动蛋白的表达及临床意义[J]. 口腔医学研究, 2019, 35(4): 393-396.
[4]	李新, 孙银银, 潘英潇, 王赛男, 张馨予, 卢恕来. 口腔扁平苔藓患者唾液中氧化应激指标与NF-κB相关炎症因子相关性的研究[J]. 口腔医学研究, 2019, 35(12): 1187-1190.
[5]	李娜, 林崇翔, 丁熙, 邵侠, 赵瑜, 屠呈威. 大鼠微螺钉种植体周围炎外周血中Foxp3⁺调节性T细胞的水平变化[J]. 口腔医学研究, 2018, 34(7): 726-729.
[6]	田原野,李洪远,李君萍,唐瞻贵. 7,12-二甲基苯并[a]蒽诱发叙利亚地鼠颊鳞状细胞癌模型中Th1/Th2、Th17/Treg平衡变化研究[J]. 口腔医学研究, 2018, 34(12): 1284-1288.
[7]	董子昱, 张芳. 口腔扁平苔藓唾液标记物研究现状分析[J]. 口腔医学研究, 2018, 34(11): 1168-1171.
[8]	任莉,韩杰,徐明明,王隽. OLP患者外周血T细胞B7-H1及PD-1的表达情况及与疾病状态的关系研究[J]. 口腔医学研究, 2017, 33(12): 1319-1322.
[9]	周辉,唐欣轶,郭燕. miR-146a在口腔扁平苔藓患者外周血及组织中表达及与IRAK1和TRAF6表达的相关性[J]. 口腔医学研究, 2016, 32(9): 949-952.
[10]	李阳,刘思佳,常缨,王婷婷,李贞,王婧娇,张敬,王丽,漆明. 白芍总苷配伍枸杞治疗口腔扁平苔藓患者的疗效评价[J]. 口腔医学研究, 2016, 32(8): 861-864.
[11]	陈冶. 白细胞相关免疫球蛋白样受体-2和转化生长因子-β在口腔扁平苔藓患者外周血表达及意义[J]. 口腔医学研究, 2016, 32(5): 513-516.
[12]	延欣虹,张波. 白芍总苷对糜烂型口腔扁平苔藓患者外周血中IFN-γ及IL-10表达的影响研究[J]. 口腔医学研究, 2016, 32(5): 534-537.
[13]	曹直. miR-155在口腔扁平苔藓患者外周血及组织中表达及意义[J]. 口腔医学研究, 2016, 32(2): 185-188.
[14]	张娜, 张静, 谭雅芹 ,杜格非 ,卢锐 ,周刚. LC3B在口腔扁平苔藓组织及其T细胞中的表达[J]. 口腔医学研究, 2016, 32(12): 1257-1260.
[15]	卢锐. 口腔扁平苔藓的目标治疗:观点和展望[J]. 口腔医学研究, 2016, 32(11): 1213-1216.