晚期糖基化终末产物AGEs通过牙周膜成纤维细胞的TLR4途径促进牙周炎症

doi:10.13701/j.cnki.kqyxyj.2020.11.006

口腔医学研究 ›› 2020, Vol. 36 ›› Issue (11): 1007-1011.DOI: 10.13701/j.cnki.kqyxyj.2020.11.006

晚期糖基化终末产物AGEs通过牙周膜成纤维细胞的TLR4途径促进牙周炎症

张询¹, 袁彩霞¹, 林园园¹, 田群丽^2*

1.杭州口腔医院平海院区国际诊疗中心浙江杭州 310000;
2.杭州口腔医院平海院区儿童口腔科浙江杭州 310000

收稿日期:2020-04-10 出版日期:2020-11-28 发布日期:2020-11-27
通讯作者: *田群丽,E-mail:tql0828@126.com
作者简介:张询(1986~ ),女,湖北仙桃人,硕士,主治医师,主要从事儿童口腔医学研究。

Advanced Glycation End Products Increase Inflammation via TLR4 Pathway in Periodontal Ligament Fibroblasts

ZHANG Xun¹, YUAN Caixia¹, LIN Yuanyuan¹, TIAN Qunli^2*

1. International Diagnosis and Treatment Center of Pinghai Campus, Hangzhou Dental Hospital, Hangzhou 310000, China;
2. Department of Children's Stomatology, Pinghai Campus, Hangzhou Dental Hospital, Hangzhou 310000, China

Received:2020-04-10 Online:2020-11-28 Published:2020-11-27

摘要/Abstract

摘要： 目的:探讨糖尿病的重要病理产物晚期糖基化终末产物(AGEs)对牙周膜成纤维细胞(PDLC)中Toll样受体4(TLR4)介导的相关炎症因子表达的作用,以阐明AGEs对牙周炎可能的影响。方法:分别使用不同剂量的AGEs(0、100、300、500 mg/L)处理牙周膜细胞。通过免疫荧光染色α-actin,以检测AGEs对细胞骨架的可能作用。通过Western blot检测不同剂量的AGEs对PLDCs表达TLR4及下游炎症因子IL-1β和TNF-α的影响,以及AGEs抑制剂E5564对TLR4激活的阻断作用。通过免疫荧光再次验证AGEs通过TLR4对IL-1β和TNF-α的激活作用。结果:AGEs对PDLCs的培养和形态并未有影响,对细胞结构蛋白α-actin的表达未见明显影响。Western blot结果显示,与对照组相比,300和500 mg/L的AGEs处理明显增加了PDLCs的TLR4的表达,且300和500 mg/L剂量之间未发现统计学差异。AGEs引起的TLR4的激活继续导致了下游IL-1β和TNF-α的表达上调,Western blot和免疫荧光均证明,加入TLR4特异性抑制剂E5564可以逆转TLR4通路诱导的IL-1β和TNF-α激活。结论:AGEs并未对成纤维细胞的形态和骨架有明显影响,AGEs可能通过TLR4通路促进牙周成纤维细胞的炎症因子IL-1β和TNF-α的释放,促进牙周炎的发展。

关键词: 糖基化终末产物, 牙周炎, Toll样受体4, 白细胞介素-1β, 肿瘤坏死因子-α

Abstract: Objective: To investigate the effect of advanced glycation end products (AGEs),a product of diabetes,on the expression of Toll-like receptor 4 (TLR4)-mediated inflammation in periodontal ligament cells (PDLC). Methods: Different doses of AGEs (0,100,300,500 mg/L) were used to treat PDLCs. α-Actin was stained by immunofluorescence staining to detect the cytoskeleton. Western blot was used to detect the effect of AGEs on the expression of TLR4 and the downstream factors IL-1β and TNF-α,as well as the blocking effect of AGEs inhibitor E5564 on TLR4 activation. Immunofluorescence confirmed the activation of IL-1β and TNF-αvia TLR4 pathway by AGEs. Results: AGEs had no effect on the culture and morphology of PDLCs, and no significant effect on the expression of cell structural protein α-Actin. 300 mg/L and 500 mg/L AGEs significantly increased the TLR4 expression compared with the control group,and no statistical difference was found between the 300 mg/L and 500 mg/L doses. The activation of TLR4 caused by AGEs continued to lead to the up-regulation of IL-1β and TNF-α. Western blot and immunofluorescence proved that the addition of TLR4-specific inhibitor E5564 could reverse the activation of IL-1β and TNF-α induced by TLR4 pathway. Conclusion: AGEs have no obvious effect on the morphology of fibroblasts. AGEs may promote the release of inflammatory factors IL-1β and TNF-α from periodontal fibroblasts through the TLR4 pathway.

Key words: AGEs, periodontitis, TLR4, IL-1β, TNF-α

张询, 袁彩霞, 林园园, 田群丽. 晚期糖基化终末产物AGEs通过牙周膜成纤维细胞的TLR4途径促进牙周炎症[J]. 口腔医学研究, 2020, 36(11): 1007-1011.

ZHANG Xun, YUAN Caixia, LIN Yuanyuan, TIAN Qunli. Advanced Glycation End Products Increase Inflammation via TLR4 Pathway in Periodontal Ligament Fibroblasts[J]. Journal of Oral Science Research, 2020, 36(11): 1007-1011.

参考文献

[1] Perrone A, Giovino A, Benny J, et al. Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects [J]. Oxid Med Cell Longev,2020,2020:3818196.
[2] Katz J, Caudle RM, Bhattacharyya I, et al. Receptor for advanced glycation end product (RAGE) upregulation in human gingival fibroblasts incubated with nornicotine [J]. J Periodontol,2005,76(7):1171-1174.
[3] Lee KJ, Yoo JW, Kim YK, et al. Advanced glycation end products promote triple negative breast cancer cells via ERK and NF-kappaB pathway [J]. Biochem Biophys Res Commun,2018,495(3):2195-2201.
[4] Qin Q, Niu J, Wang Z, et al. Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway [J]. Cardiovasc Diabetol,2013,12:37.
[5] Qi W, Yang X, Ye N, et al. TLR4 gene in the regulation of periodontitis and its molecular mechanism [J]. Exp Ther Med,2019,18(3):1961-1966.
[6] Korneev KV, Atretkhany KN, Drutskaya MS, et al. TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis [J]. Cytokine,2017,89:127-135.
[7] Takeda K, Akira S. TLR signaling pathways [J]. Semin Immunol,2004,16(1):3-9.
[8] Gurav A, Jadhav V. Periodontitis and risk of diabetes mellitus [J]. J Diabetes,2011,3(1):21-28.
[9] Ren L, Fu Y, Deng Y, et al. Advanced glycation end products inhibit the expression of collagens type I and III by human gingival fibroblasts [J]. J Periodontol,2009,80(7):1166-1173.
[10] Choi AJ, Ryter SW. Inflammasomes: molecular regulation and implications for metabolic and cognitive diseases [J]. Mol Cells,2014,37(6):441-448.
[11] Zhang Z, Liu Q, Liu M, et al. Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II [J]. J Neuroinflammation,2018,15(1):27.
[12] Zhu YJ, Wang C, Song G, et al. Toll-like receptor-2 and -4 are associated with hyperlipidemia [J]. Mol Med Rep,2015,12(6):8241-8246.
[13] Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes [J]. Cell,2014,157(5):1013-1022.
[14] Chen X, Gao Q, Zhou L, et al. MiR-146a alleviates inflammation of acute gouty arthritis rats through TLR4/MyD88 signal transduction pathway [J]. Eur Rev Med Pharmacol Sci,2019,23(21):9230-9237.
[15] Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases [J]. Blood,2011,117(14):3720-3732.
[16] Netea MG, Simon A, van de Veerdonk F, et al. IL-1beta processing in host defense: beyond the inflammasomes [J]. PLoS Pathog,2010,6(2):e1000661.
[17] Barbara JA, Van ostade X, Lopez A. Tumour necrosis factor-alpha (TNF-alpha): the good, the bad and potentially very effective [J]. Immunol Cell Biol,1996,74(5):434-443.
[18] Ahmad R, Shihab PK, Thomas R, et al. Increased expression of the interleukin-1 receptor-associated kinase (IRAK)-1 is associated with adipose tissue inflammatory state in obesity [J]. Diabetol Metab Syndr,2015,7:71.

晚期糖基化终末产物AGEs通过牙周膜成纤维细胞的TLR4途径促进牙周炎症

Advanced Glycation End Products Increase Inflammation via TLR4 Pathway in Periodontal Ligament Fibroblasts

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]	周岳, 申玉芹. 透明质酸凝胶联合Nd:YAG激光对老年牙周炎患者牙根敏感的实验研究及临床疗效观察[J]. 口腔医学研究, 2021, 37(1): 39-42.
[2]	鲁皓, 李金凤, 苏旭, 戴江红, 陈晓涛. 负性情绪与慢性牙周炎的相关性研究[J]. 口腔医学研究, 2021, 37(1): 43-47.
[3]	刘悦, 王雷. 他汀类药物与牙周炎关系的研究进展[J]. 口腔医学研究, 2020, 36(9): 811-813.
[4]	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.
[5]	王琳璇, 王琦, 赵云, 刘一鸣, 韩梅, 米方林. TNF-α对牙周膜成纤维细胞ephrinB2/EphB4表达量的影响[J]. 口腔医学研究, 2020, 36(8): 741-744.
[6]	齐晓爽, 孟维艳. 用于牙周炎治疗的自噬调节物研究现状[J]. 口腔医学研究, 2020, 36(7): 616-618.
[7]	王昆于, 孙毓言, 张慧彦, 齐晓爽, 张震阳, 乔树伟, 向镜成, 丁佳鑫, 孟维艳. 负载D-缬氨酸水凝胶对大鼠实验性牙周炎的影响[J]. 口腔医学研究, 2020, 36(7): 658-663.
[8]	刘君瑜, 肖宇, 王翔宇, 刘艳, 李玉芳, 柳海凤, 陈宇, 包崇云. 血糖敏感型水凝胶治疗糖尿病大鼠牙周炎的实验研究[J]. 口腔医学研究, 2020, 36(6): 567-571.
[9]	吴芸菲, 张黎, 张旭凤, 符起亚. 烟草提取物辅酶Q10对牙周炎小鼠Treg/T17细胞免疫平衡的影响[J]. 口腔医学研究, 2020, 36(6): 572-576.
[10]	周伟, 汤雅, 李厚轩. 南京地区侵袭性牙周炎近6年就诊情况调查分析[J]. 口腔医学研究, 2020, 36(5): 473-476.
[11]	臧文丽, 刘俊超, 潘亚萍. 丁酸对牙周炎的影响机制研究进展[J]. 口腔医学研究, 2020, 36(4): 318-320.
[12]	田源, 陈靖, 曾凤娇, 于航, 刘霞, 刘建国, 白国辉. SD大鼠经鼻黏膜免疫牙周炎基因疫苗pVAX1-HA2-FimA-(IL-15)后Tfh细胞的变化[J]. 口腔医学研究, 2020, 36(4): 350-354.
[13]	丁小函, 岳轶云, 夏博园, 李艳, 刘歆婵, 武洲, 于维先. Mongersen对大鼠牙周炎抗炎效果观察[J]. 口腔医学研究, 2020, 36(4): 382-386.
[14]	杨磊, 郭留云, 程志芬, 李碧浩. Shh蛋白与慢性牙周炎炎症程度的相关性研究[J]. 口腔医学研究, 2020, 36(2): 131-134.
[15]	韩亚琨, 于程程, 于艳. 牙周炎宿主转化生长因子-β⁺调节性B细胞变化特点[J]. 口腔医学研究, 2020, 36(2): 135-138.