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

doi:10.12259/j.issn.2095-610X.S20241107

TLR4/NF-κB/ MUC5B在过敏性鼻炎中的调控机制

doi: 10.12259/j.issn.2095-610X.S20241107

1.
康复大学青岛中心医院头颈外科
2.
门诊部，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
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- 文章访问数: 296
- HTML全文浏览量: 230
- PDF下载量: 14
- 被引次数: 0
出版历程
- 收稿日期: 2024-06-10
- 网络出版日期: 2024-10-23
- 刊出日期: 2024-11-25

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

1.
Dept. of Head and Neck Surgery
2.
Dept. of Outpatient，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。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）。结论发现TLR4/NF-κB/ MUC5B在过敏性鼻炎中的调控作用，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. 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：IFN-γ，IL-4，IL-10和TNF-α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：IFN-γ，IL-4，IL-10和TNF-α在组织中的水平变化；^*P < 0.05，^**P < 0.01，^***P < 0.001，ns not significant。

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

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参考文献(29)

[1]	Hoyte F C L,Nelson H S. Recent advances in allergic rhinitis[J]. F1000Res,2018,7(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]	Geng B, Dilley M, Anterasian C. Biologic therapies for allergic rhinitis and nasal polyposis[J]. Curr Allergy Asthma Rep,2021,21(6):36.
[6]	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
[7]	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
[8]	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
[9]	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.
[10]	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
[11]	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.
[12]	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.
[13]	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
[14]	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
[15]	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
[16]	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.
[17]	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
[18]	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
[19]	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
[20]	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
[21]	Tak P P,Firestein G S. NF-kappa B: A key role in inflammatory diseases[J]. J Clin Invest,2001,107(1):7-11. doi: 10.1172/JCI11830
[22]	Lawrence T. The nuclear factor NF-kappaB pathway in inflammation[J]. Cold Spring Harb Perspect Biol,2009,1(6):a001651.
[23]	Poma P. NF-κB and disease[J]. Int J Mol Sci,2020,21(23):81-91.
[24]	Bousquet J, Anto J M, Bachert C, et al. Allergic rhinitis[J]. Nat Rev Dis Primers,2020,6(1):95.
[25]	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
[26]	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.
[27]	Tian B, Ma X, Jiang R. Daphnetin mitigates ovalbumin-induced allergic rhinitis in mice by regulating Nrf2/HO-1 and TLR4/NF-kB signaling[J]. Am J Rhinol Allergy,2023,37(1):19-25.
[28]	Piao C H, Fan Y, Nguyen T V, et al. PM2.5 exposure regulates Th1/Th2/Th17 cytokine production through NF-κB signaling in combined allergic rhinitis and asthma syndrome[J]. Int Immunopharmacol,2023,119(1):110-254.
[29]	Zhao H, Yang J, Wang M, et al. Effect of IL-9 neutralising antibody on pyroptosis via SGK1/NF-κB/NLRP3/GSDMD in allergic rhinitis mice[J]. Biomed Pharmacother,2024,177(1):117-119.

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