TLR4/NF-κB/ MUC5B在过敏性鼻炎中的调控机制

王阿衡; 宋镇; 杨广华; 何海燕

TLR4/NF-κB/ MUC5B在过敏性鼻炎中的调控机制

1.
康复大学青岛中心医院头颈外科
2.
门诊护士，山东青岛　266000

基金项目: 青岛市科技惠民专项基金资助项目（24-2-8smjk-12-nsh）。

详细信息

作者简介:
王阿衡（1992～），女，山东青岛人，医学硕士，住院医师，主要从事鼻科学临床诊疗工作

通讯作者:
何海燕，E-mail：hhyy3027@163.com

中图分类号: R765.21
计量
- 文章访问数: 30
- HTML全文浏览量: 24
- PDF下载量: 1
- 被引次数: 0
出版历程

Regulatory Mechanisms of TLR4/NF-κB/ MUC5B in Allergic Rhinitis

1.
Dept. of Head and Neck Surgery
2.
Dept. of Outpatient Nursing，Qingdao Central Hospital of Rehabilitation University，Qingdao Shandong 266000，China

摘要

摘要: 目的探讨TLR4/NF-κB/ MUC5B在过敏性鼻炎中的调控机制，为这类疾病提供新的治疗策略。方法建立过敏性鼻炎小鼠模型，观察模型病理特征变化，检测TLR4和MUC5B的表达。通过鼻内给药的方式降低TLR4的表达，观察组织病理变化，MUC5B的表达以及炎症因子浓度的变化。建立体外细胞模型，通过细胞转染，敲减TLR4后，检测MUC5B的表达，以及观察NF-κB和磷酸化NF-κB（p-NF-κB）的变化。结果（1）TLR4和MUC5B在过敏性鼻炎小鼠模型中高表达（P < 0.05）；（2）降低TLR4的表达可减少MUC5B和炎症因子的表达，以及缓解过敏性鼻炎（P < 0.05）；（3）在体外，敲减TLR4，可降低p-NF-κB和MUC5B的表达（P < 0.05）。结论 TLR4/NF-κB/ MUC5B在过敏性鼻炎中控作用，为治疗过敏性鼻炎提供新的思路。
- 过敏性鼻炎 /
- TLR4 /
- MUC5B /
- NF-κB
Abstract: Objective To explore the regulatory mechanism of TLR4/NF-κB/MUC5B in allergic rhinitis so as to provide a new therapeutic strategy for this type of disease. Methods A mouse model of allergic rhinitis was established to observe the changes in pathological characteristics of the model and to detect the expression of TLR4 and MUC5B. By reducing the expression of TLR4 by intranasal administration, the histopathological changes of TLR4, the expression of MUC5B and the concentration of inflammatory factors were observed. An in vitro cell model was established to detect the expression of MUC5B as well as to observe the changes of NF-κB and phosphorylated NF-κB （p-NF-κB） after knockdown of TLR4 by cell transfection. Results （1） TLR4 and MUC5B were highly expressed in a mouse model of allergic rhinitis （P < 0.05）;（2） Lowering the expression of TLR4 could reduce the expression of MUC5B and inflammatory factors, as well as alleviated allergic rhinitis （P < 0.05）; （3） In vitro, knockdown of TLR4 could reduce the expression of p-NF-κB and MUC5B （P < 0.05）. Conclusion The regulatory mechanism of TLR4/NF-κB/ MUC5B in allergic rhinitis provides the new ideas for the treatment of allergic rhinitis.
- Allergic rhinitis /
- TLR4 /
- MUC5B /
- NF-κB

HTML全文

图 1 AR小鼠模型中MUC5B，TLR4和炎症因子的表达

A：HE染色检测鼻粘膜病理变化；B：IL-10，IL-4，TNF-α和IFN-γ在组织中的表达；C：MUC5B在组织中的阳性率；D：TLR4在组织中的阳性率；E：MUC5B和TLR4的阳性率的统计学分析；^*P<0.05，^**P<0.01。

Figure 1. Expression of MUC5B，TLR4 and inflammatory factors in an AR mouse model

下载: 全尺寸图片幻灯片

图 2 TLR4敲减对小鼠AR和炎症因子的影响

A：qPCR检测TLR4的表达；B：HE检测不同组的病理变化；C：IL-10，IL-4，TNF-α和IFN-γ在组织中的水平变化；^*P < 0.05，^**P < 0.01，^***P < 0.001。

Figure 2. Effects of TLR4 knockdown on AR and inflammatory factors in mice

下载: 全尺寸图片幻灯片

图 3 TLR4通过NF-κB调控MUC5B的表达

A：qPCR检测TLR4的表达；B：Western blot检测MUC5B的表达；C：Western blot检测NF-κB通路表达变化；^*P < 0.05，^**P < 0.01，^***P < 0.001。

Figure 3. TLR4 regulates MUC5B expression through NF-κB

下载: 全尺寸图片幻灯片

参考文献(25)

[1]	Hoyte F C L,Nelson H S. Recent advances in allergic rhinitis[J]. F,1000,Res,2018,7(1):18,7(1): 1.
[2]	Cohen B. Allergic Rhinitis[J]. Pediatr Rev,2023,44(10):537-550. doi: 10.1542/pir.2022-005618
[3]	Skoner D P. Complications of allergic rhinitis[J]. J Allergy Clin Immunol,2000,105(6 Pt 2): S605-609.
[4]	Chirakalwasan N,Ruxrungtham K. The linkage of allergic rhinitis and obstructive sleep apnea[J]. Asian Pac J Allergy Immunol,2014,32(4):276-286.
[5]	Park B S,Lee J O. Recognition of lipopolysaccharide pattern by TLR4 complexes[J]. Exp Mol Med,2013,45(12):e66. doi: 10.1038/emm.2013.97
[6]	Yang L,Lian Z,Zhang B,et al. Effect of ligustrazine nanoparticles on Th1/Th2 balance by TLR4/MyD88/NF-κB pathway in rats with postoperative peritoneal adhesion[J]. BMC Surg,2021,21(1):211. doi: 10.1186/s12893-021-01201-7
[7]	Wu J,Wu L,Zhang L,et al. Overexpression of miR-224-5p alleviates allergic rhinitis in mice via the TLR4/MyD88/NF-κB pathway[J]. Exp Anim,2021,70(4):440-449. doi: 10.1538/expanim.20-0195
[8]	Siddiqui Z A,Walker A,Pirwani M M,et al. Allergic rhinitis: Diagnosis and management[J]. Br J Hosp Med (Lond),2022,83(2):1-9.
[9]	Lim K H,Staudt L M. Toll-like receptor signaling[J]. Cold Spring Harb Perspect Biol,2013,5(1):a011247. doi: 10.1101/cshperspect.a011247
[10]	Veneziani I,Alicata C,Moretta L,et al. Human toll-like receptor 8 (TLR8) in NK cells: Implication for cancer immunotherapy[J]. Immunol Lett,2023,261(1):13-16.
[11]	Kang C,Li X,Liu P,et al. Tolerogenic dendritic cells and TLR4/IRAK4/NF-κB signaling pathway in allergic rhinitis[J]. Front Immunol,2023,14(1):1276512.
[12]	Chen S N,Tan Y,Xiao X C,et al. Deletion of TLR4 attenuates lipopolysaccharide-induced acute liver injury by inhibiting inflammation and apoptosis[J]. Acta Pharmacol Sin,2021,42(10):1610-1619. doi: 10.1038/s41401-020-00597-x
[13]	Tam J S Y,Coller J K,Hughes P A,et al. Toll-like receptor 4 (TLR4) antagonists as potential therapeutics for intestinal inflammation[J]. Indian J Gastroenterol,2021,40(1):5-21. doi: 10.1007/s12664-020-01114-y
[14]	Huang X,Guan W,Xiang B,et al. MUC5B regulates goblet cell differentiation and reduces inflammation in a murine COPD model[J]. Respir Res,2022,23(1):11. doi: 10.1186/s12931-021-01920-8
[15]	李增沛,李靖. 变应性鼻炎患者TNF-α、Tim-1及TLR4变化与病情程度的相关性研究[J]. 中国耳鼻咽喉颅底外科杂志,2023,29(6):50-53.
[16]	Dong J,Xu O,Wang J,et al. Luteolin ameliorates inflammation and Th1/Th2 imbalance via regulating the TLR4/NF-κB pathway in allergic rhinitis rats[J]. Immunopharmacol Immunotoxicol,2021,43(3):319-327. doi: 10.1080/08923973.2021.1905659
[17]	唐进渝,彭丽娟,钟春燕,等. 慢性鼻-鼻窦炎患者HIF-1α、FoxM1的表达及其与黏蛋白MUC5AC、MUC5B的相关性[J]. 西部医学,2023,35(11):1610-1614. doi: 10.3969/j.issn.1672-3511.2023.11.009
[18]	龙小博,甄宏韬,彭璐等. 布地奈德对变应性鼻炎鼻黏膜黏蛋白MUC5AC和MUC5B表达的影响[J]. 华中科技大学学报(医学版),2007,36(5):648-651,704. doi: 10.3870/j.issn.1672-0741.2007.05.024
[19]	Płóciennikowska A,Hromada-Judycka A,Borzęcka K,et al. Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling[J]. Cell Mol Life Sci,2015,72(3):557-581. doi: 10.1007/s00018-014-1762-5
[20]	Tak P P,Firestein G S. NF-kappaB: A key role in inflammatory diseases[J]. J Clin Invest,2001,107(1):7-11. doi: 10.1172/JCI11830
[21]	Lawrence T. The nuclear factor NF-kappaB pathway in inflammation[J]. Cold Spring Harb Perspect Biol,2009,1(6):a001651.
[22]	Poma P. NF-κB and disease[J]. Int J Mol Sci,2020,21(23):81-91.
[23]	基于NF-κB信号通路探讨小青龙汤合玉屏风散对变应性鼻炎大鼠MUC5AC和MUC5B表达的影响辽宁中医药大学学报[J]. 辽宁中医药大学学报,2016,18(6): 3.
[24]	牛金明,程莉雅,吴美美. 柚皮素对过敏性鼻炎模型大鼠鼻黏膜组织TLR4/NF-κB/TNF-α信号通路的影响[J]. 中国实验诊断学,2023,27(4):483-488. doi: 10.3969/j.issn.1007-4287.2023.04.027
[25]	Zhu X,Sun Y,Yu Q,et al. Exosomal lncRNA GAS5 promotes M1 macrophage polarization in allergic rhinitis via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling[J]. Int Immunopharmacol,2023,121(1):110-450.

相关文章(20)

[1]	付怡丹, 陈文婷, 苏晓杨, 赵燕, 兰丹凤, 杨秋萍. Mertk介导NF-κb通路影响雪旺细胞炎症反应的作用, 昆明医科大学学报. 2023, 44(12): 20-24. doi: 10.12259/j.issn.2095-610X.S20231203
[2]	朱婷娜, 曹媛媛, 张园, 刘鹏亮, 王一航, 吴亚梅, 李利华, 赵永娜, 洪仕君. 不同剂量天麻素对甲基苯丙胺依赖CPP大鼠海马中TLR4/MyD88/NF-κB炎症信号通路的影响, 昆明医科大学学报. 2023, 44(2): 33-39. doi: 10.12259/j.issn.2095-610X.S20230226
[3]	张园, 朱婷娜, 曹媛媛, 刘鹏亮, 王一航, 吴亚梅, 李利华, 赵永娜, 洪仕君. TLR4/MyD88/NF-κB 信号通路对甲基苯丙胺依赖CPP大鼠海马的影响, 昆明医科大学学报. 2023, 44(2): 7-13. doi: 10.12259/j.issn.2095-610X.S20230225
[4]	皮娜, 何琴, 钟燕, 靳璇, 朱振东, 张旋. 滇龙胆草对肺纤维化小鼠肺组织NF-κB和CTGF表达的影响, 昆明医科大学学报. 2021, 42(4): 8-12. doi: 10.12259/j.issn.2095-610X.S20210402
[5]	李志强, 高红强, 李镜锋, 余杰琦, 王冬冬, 陈刚, 褚光. ICAM-1、MMP-9及NF-κB在胆管癌中的表达及与外周血免疫抑制细胞的关系, 昆明医科大学学报. 2021, 42(11): 93-98. doi: 10.12259/j.issn.2095-610X.S20211117
[6]	刘俊, 和红兵, 任晓斌. 云南白药对LPS诱导小鼠头颅骨炎症模型NF-κ B和NFATc1的影响, 昆明医科大学学报. 2019, 40(07): 7-14.
[7]	路轶晴. CYP4A11和载脂蛋白B、E基因多态性与原发性高血压患病风险的相关性, 昆明医科大学学报. 2018, 39(05): 70-77.
[8]	沈志祥, 朱立勋, 徐伟红. 有氧运动对2型糖尿病大鼠AGE-RAGE轴及NF-κB通路的影响, 昆明医科大学学报. 2018, 39(01): 16-19.
[9]	杨金凤, 蒙国懿, 黄兆奎, 洪仕君, 李利华, 邢豫明, 赵永娜. 甲基苯丙胺对大鼠海马5-HT、IL-6及NF-κB表达的影响, 昆明医科大学学报. 2018, 39(07): 5-9.
[10]	汤伟伟, 何永文. NF-κB和TAB3在口腔鳞状细胞癌组织中的表达及临床意义, 昆明医科大学学报. 2018, 39(10): 42-45.
[11]	廖然超, 余咏梅, 邱吉蔚, 徐学梅. 昆明地区过敏性鼻炎及哮喘患者家庭优势尘螨种类调查, 昆明医科大学学报. 2017, 38(06): 56-59.
[12]	张金培, 杨屹, 靳艳. 麻芎舒痛方治疗偏头痛的临床效果及对血清5-HT、NF-κB和炎症因子水平的影响, 昆明医科大学学报. 2017, 38(08): 40-43.
[13]	杨蓉, 杨莹. 巨噬细胞中oxLDL对TLR4-Src信号通路激活的调控, 昆明医科大学学报. 2017, 38(05): 44-49.
[14]	陈鑫, 黄璞, 贾楠楠, 陈绍春, 叶频, 刘承杏, 李国萍. 鼻咽癌细胞株CNE-2及其亚克隆S-18裸鼠皮下移植生长速度比较, 昆明医科大学学报. 2016, 37(12): 8-11.
[15]	刘晓晨. 昆明地区大学生过敏性鼻炎问卷调查, 昆明医科大学学报. 2016, 37(08): -.
[16]	贾楠楠. Gnaq对SH-SY5Y细胞增殖的作用及机制, 昆明医科大学学报. 2016, 37(01): -.
[17]	廖然超. 过敏性喉炎1例, 昆明医科大学学报. 2015, 36(04): -1.
[18]	杨乐. 过敏性鼻炎合并支气管哮喘或慢性咳嗽37例临床治疗分析, 昆明医科大学学报. 2015, 36(01): -1.
[19]	马珊. 凉血活血药物对氧诱导小鼠视网膜新生血管实验中HIF-1和NF-κB的影响, 昆明医科大学学报. 2012, 33(10): 1-1.
[20]	. 成人过敏性紫癜32例临床分析, 昆明医科大学学报. 2011, 32(03): -.