[1]薛璐,侯淑萍,单士军,等.特应性皮炎小鼠模型VDRAs对TLR2,TLR4及CRAMP的调控作用[J].中国皮肤性病学杂志,2017,(04):369-374.[doi:10.13735/j.cjdv.1001-7089.201609103]
　XUE Lu,HOU Shu-ping,SHAN Shi-jun,et al.Regulation of TLR2, TLR4 and CRAMP with VDRAs in Atopic Dermatitis Model Mice[J].The Chinese Journal of Dermatovenereology,2017,(04):369-374.[doi:10.13735/j.cjdv.1001-7089.201609103]
点击复制

特应性皮炎小鼠模型VDRAs对TLR2,TLR4及CRAMP的调控作用
分享到：

《中国皮肤性病学杂志》[ISSN:1001-7089/CN:61-1197/R]

卷:
期数:
2017年04期
页码:
369-374
栏目:
论著
出版日期:
2017-04-01

文章信息/Info

Title:
Regulation of TLR2, TLR4 and CRAMP with VDRAs in Atopic Dermatitis Model Mice
作者:
薛璐;  侯淑萍;  单士军;  罗素菊;  岑醒洪;  王迪;  刘原君;  王惠平
天津医科大学总医院皮肤性病科,天津 300052
Author(s):
XUE Lu; HOU Shu-ping; SHAN Shi-jun; LUO Su-ju; CEN Xing-hong; WANG Di; LIU Yuan-jun; WANG Hui-ping
Department of Dermatology and Venereology,Tianjin Medical University General Hospital,Tianjin 300052,China
关键词:
特应性皮炎;  维生素受体激动剂;  Toll受体2;  Toll受体4;  鼠阳离子相关抗菌肽
Keywords:
Atopic dermatitis;  Vitamin D receptor activators;  TLR2;  TLR4;  CRAMP
分类号:
R 758.2
DOI:
10.13735/j.cjdv.1001-7089.201609103
文献标志码:
A
摘要:
目的 观察在特应性皮炎(AD)小鼠模型中维生素D受体激动剂(VDRAs)的干预对皮损以及Toll受体2,4(TLR2,TLR4)和鼠阳离子相关抗菌肽(CRAMP)的影响,并探讨其相互关联机制。方法 将25只雌性BALB / c 小鼠随机分为5组,分别为空白组、AD模型组、AD模型不干预组、PBS对照组、VDRAs治疗组,每组各5只。除空白组以外的其余4组,以二硝基氯苯(DNCB)诱导小鼠特应性皮炎模型。造模成功后,模型组直接处死,AD模型不干预组造模结束后不予以任何处理,VDRAs治疗组腹腔注射VDRAs,PBS对照组腹腔注射PBS液,两组均为每3日1次,总计5次。肉眼观察小鼠背部皮损变化,组织病理观察皮损厚度及炎细胞浸润情况。免疫组化观察各组皮损处TLR2,TLR4及CRAMP的表达部位及水平。Real-Time PCR测各组皮损中TLR2,TLR4及CRAMP的RNA含量,定量分析其变化。结果 VDRAs治疗组小鼠背部皮损炎症反应较AD模型不干预组和PBS对照组明显改善,免疫组化和Real-Time PCR示CRAMP的表达高于AD模型不干预组和PBS对照组,TLR2,TLR4表达较PBS对照组和AD模型组低,差异有统计学意义(P<0.01)。结论 在AD小鼠模型中,VDRAs抑制TLR2,TLR4表达,上调抗菌肽CRAMP的表达。
Abstract:
Objective To detect the effect of vitamin D receptor agonist(VDRAs)on skin lesions improvement and the expression level of toll receptor 2,4(TLR2, TLR4), the antimicrobial peptide CRAMP in atopic dermatitis(AD)model mice, and to explore their inter-related mechanisms. Methods Twenty-five female BABL/c mice were randomly and equally divided into 5 groups: control group, AD model group, AD model no processing group, PBS-control group, VDRAs intervention group. Five mice in each group. The atopic dermatitis(AD)model mice were induced by dinitrochlorobenzene(DNCB)except the control group. After modeling, the AD group were sacrificed. The PBS-control group received intraperitoneal injection of PBS, the VDRAs group received intraperitoneal injection of VDRAs, once every three days, total 5 times. At the end of treatment, the changes of the skin lesions and pathologic condition of the five group mice were detected. The expression and the localization of TLR2, TLR4 and CRAMP in skin lesions were detected through immunohistochemical staining. Real-Time PCR were performed to detect the mRNA expression level of TLR2, TLR4 and CRAMP in serum. Results After treatment with VDRAs, the inflammatory reaction show significantly improvement and the expression level of CRAMP mRNA in serum was increased in VDRAs treatment group compared with the AD model no processing group and the PBS-control. In contrast, the expression level of TLR2 and TLR4 mRNA were decreased compared with the AD model no processing group and the PBS-control(P<0.01). Conclusion In the AD model mice, VDRAs can down-regulate the expression level of TLR2, TLR4 and up-regulate the expression level of antimicrobial peptides CRAMP.

参考文献/References:

[1] Zhang R,Zhou M,Wang L,et al.Phylloseptin-1( PSN-1)from phyllomedusa sauvagei skin secretion:A novel broadspectrum antimicrobial peptide with antibiofilm activity[J].Mol Immunol,2010,47(11-12):2030-2037.
[2] Jia Sun, Laetitia Furio, Ramine Mecheri,et al.Pancreatic β-cells limit autoimmune diabetes via an immunoregulatory antimicrobial peptide expressed under the influence of the gut microbiota[J].Immunity, 2015,43(2):304-317.
[3] Elisabeth Roider, Thomas Ruzicka, Jürgen Schauber.Vitamin D, the cutaneous barrier, antimicrobial peptides and allergies: Is there a link?[J].Allergy Asthma Immunol Res,2013,5(3):119-128.
[4] Tsybikov NN, Petrisheva I, Fefelova EV,et al.Expression of TLR2 and TLR4 on peripheral blood monocytes during exacerbation of atopic dermatitis[J]. Allergy and Asthma Proceedings, 2015, 36(6):e140-145.
[5] Soon Re Kim, Han-Seok Choi, Hye Sook Seo, et al.Topical application of herbal mixture extract inhibits ovalbumin-or 2,4-dinitrochlorobenzene-induced atopic dermatitis[J].Hindawi Publishing Corporationdoi,2012,2012:545497.
[6] Heimbeck I,Wjst M,Apfelbacher CJ. Low vitamin D serum level is inversely associated with eczema in children and adolescents in Germany[J]. Allergy,2013,68(7):906-910.
[7] 李絮茹,岑醒洪,毕田田,等.维生素D受体激动剂对模型小鼠特应性皮炎的治疗作用[J].中国皮肤性病学杂志,2015,29(2):133-136.
[8] Jun S.VitaminD and mucosal immune function[J].Curr Opin Gastroenterol,2010,26( 6):591-595.
[9] Boguniewicz M, Leung DY.Atopic dermatitis: a disease of altered skin barrier and immune dysregulation[J].Immunol Rev, 2011,242(1): 233-246.
[10] Park JH,Park GT,Cho IH,et al.An antimicrobial protein,lactoferrin exists in the sweat:proteomic analysis of sweat[J].Exp Dennatol,2011,20(10):369-371.
[11] 蔡林,孙青苗.抗菌肽与皮肤疾病关系的研究进展[J].中国皮肤性病学杂志,2011,25(1):1-5.
[12] Kanda N, Hau CS, Tada Y, et al.Decreased serum LL-37 and vitamin D3 levels in atopic dermatitis: relationship between IL-37 and oncostatin M [J].Allergy, 2012, 67(6): 804-812.
[13] Kyungho Park, Sinhee Lee, Yong-Moon, et al.Lee sphingolipids and antimicrobial peptides: function and roles in atopic dermatitis[J].Biomol Ther,2013,21(4): 251-257.
[14] Sugitharini V, Shahana P, Prema A,et al.TLR2 and TLR4 coactivation utilizes distinct signaling pathways for the production of Th1/Th2/Th17 cytokines in neonatal immune cells[J].Cytokine,2016,24(6):191-200.
[15] Panzer R, Blobel C, Fölster-Holst R, et al.TLR2 and TLR4 expression in atopic dermatitis,contact dermatitis and psoriasis[J].Experimental Dermatology, 2014,23(5):364-366.

相似文献/References:

[1]于晓虹,宋智琦,刘晓明,等.0.1%他克莫司软膏诱发Kaposi水痘样疹1例[J].中国皮肤性病学杂志,2012,(08):757.
[2]李絮茹,岑醒洪,毕田田,等.维生素D受体激动剂对模型小鼠特应性皮炎的治疗作用[J].中国皮肤性病学杂志,2015,(02):133.[doi:10.13735/j.cjdv.1001-7089.201408080]
　LI Xu ru,CEN Xing hong,BI Tian tian,et al.Effects of Vitamin D Receptor Activators on Atopic Dermatitis Model Mice[J].The Chinese Journal of Dermatovenereology,2015,(04):133.[doi:10.13735/j.cjdv.1001-7089.201408080]
[3]闫毅,蔡莉,陈婷,等.308nm单频准分子光与311nm窄谱中波紫外线照射治疗特应性皮炎的临床疗效比较[J].中国皮肤性病学杂志,2015,(03):251.[doi:10.13735/j.cjdv.1001-7089.201407110]
　YAN Yi,CAI Li,CHEN Ting,et al.Comparison of Efficacy of 308 nm Monochromatic Excimer Light and 311 nm Narrowband Ultraviolet for the Treatment of Atopic Dermatitis[J].The Chinese Journal of Dermatovenereology,2015,(04):251.[doi:10.13735/j.cjdv.1001-7089.201407110]
[4]胡海友,王忠永,董大群,等.特应性皮炎的表观遗传研究进展[J].中国皮肤性病学杂志,2015,(04):412.[doi:10.13735/j.cjdv.1001-7089.201404094]
　HU Hai you,WANG Zhong yong,DONG Da qun,et al.Progree of Epigenetic Mechanisms in Atopic Dermatitis[J].The Chinese Journal of Dermatovenereology,2015,(04):412.[doi:10.13735/j.cjdv.1001-7089.201404094]
[5]王娟,王芳宇.激肽释放酶与特应性皮炎的关系研究进展[J].中国皮肤性病学杂志,2015,(05):524.[doi:10.13735/j.cjdv.1001-7089.201403041]
　WANG Juan,WANG Fang yu.The Research Progress of Relationships between Kallikreins and Atopic Dermatitis[J].The Chinese Journal of Dermatovenereology,2015,(04):524.[doi:10.13735/j.cjdv.1001-7089.201403041]
[6]刘苏俊,徐舰,赵斌,等.非标记定量技术检测特应性皮炎患儿尿液中差异蛋白的应用[J].中国皮肤性病学杂志,2015,(06):640.[doi:10.13735/j.cjdv.1001-7089.201404102]
　LIU Su jun,XU Jian,ZHAO Bin,et al.Application of Labelfree Quantitative Proteomics in Study Differentially Expressed Urinary Proteins in Patients with Atopic Dermatitis[J].The Chinese Journal of Dermatovenereology,2015,(04):640.[doi:10.13735/j.cjdv.1001-7089.201404102]
[7]赵巍,刘俊峰,陈达灿,等.半抗原诱导特应性皮炎小鼠模型的研究进展[J].中国皮肤性病学杂志,2015,(08):855.[doi:10.13735/j.cjdv.1001-7089.201407156]
　ZHAO Wei,LIU Jun feng,CHEN Da can,et al.Advances of Hapteninduced Murine Model of Atopic Dermatitis[J].The Chinese Journal of Dermatovenereology,2015,(04):855.[doi:10.13735/j.cjdv.1001-7089.201407156]
[8]兰元翎,杨高云.CKLF1及其拮抗肽C19在不同时期特应性皮炎患者外周血T细胞亚群中的作用[J].中国皮肤性病学杂志,2015,(10):1000.[doi:10.13735/j.cjdv.1001.7089.201502096]
　LAN Yuan-ling,YANG Gao yun.Effect of Chemokine like Factor 1 (CKLF1) and CKLF1 Antagonism Peptides C19 on Subsets of Peripheral T Cells of Atopic Dermatitis[J].The Chinese Journal of Dermatovenereology,2015,(04):1000.[doi:10.13735/j.cjdv.1001.7089.201502096]
[9]瞿旻晔,袁晓琳,马健.特应性皮炎发病过程及其机制研究现状探讨[J].中国皮肤性病学杂志,2015,(10):1085.[doi:10.13735/j.cjdv.1001.7089.201411037]
　QU Min ye,YUAN Xiao lin,MA Jian.Current Research on Pathogenesis and Mechanism of Atopic Dermatitis[J].The Chinese Journal of Dermatovenereology,2015,(04):1085.[doi:10.13735/j.cjdv.1001.7089.201411037]
[10]王敏华,艾志琼,黄玲,等.大理市3～19岁儿童及青少年特应性皮炎现况调查[J].中国皮肤性病学杂志,2015,(11):1184.[doi:10.13735/j.cjdv.1001-7089.201412051]
　WANG Min hua,AI Zhi qiong,HUANG Ling,et al.The Prevalence Study of Atopic Dermatitis among Children and Teenagers Aged 3~19 Years in Dali[J].The Chinese Journal of Dermatovenereology,2015,(04):1184.[doi:10.13735/j.cjdv.1001-7089.201412051]

备注/Memo

备注/Memo:
[基金项目] 国家自然科学基金青年科学基金项目(81301469)
[通讯作者] 王惠平,E-mail:huiping1208@163.com
更新日期/Last Update: 2017-04-05