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杏贝凝胶通过ERK-DNMT途径调节CD4+ T细胞中IFN-γ基因启动子甲基化来改善变应性鼻炎

Xingbi Gel Ameliorates Allergic Rhinitis by Regulating IFN-γ Gene Promoter Methylation in CD4+ T Cells the ERK-DNMT Pathway.

作者信息

Ai Si, Lin Yueyong, Zheng Jian, Zhuang Xiangli

机构信息

The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China.

No. 900 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Fuzhou, China.

出版信息

Front Surg. 2021 Feb 15;7:619053. doi: 10.3389/fsurg.2020.619053. eCollection 2020.

Abstract

Allergic rhinitis (AR) is a common, non-infectious, chronic nasal mucosal disease primarily mediated by immunoglobulin E (IgE) following allergen exposure. Currently, studies on AR mainly focus on cytokines, IgE and its receptors, basophils, eosinophils, mast cells, and related genes. Among these, an imbalance between T helper (Th) 1 and Th2 cells is considered an important mechanism underlying AR pathogenesis. The most important cytokines in AR are interleukin (Il)-4 and interferon gamma (IFN-γ) which are secreted by Th2 and Th1 cells, respectively. Il-4 and IFN-γ are antagonistic to each other in regulating IgE synthesis. In this study, the expression of extracellular signal-regulated protein kinase (ERK) 1/2 and its phosphorylation from p-ERK1/2, were significantly increased in a cluster of differentiation of 4+ T cells of AR mice, suggesting that the ERK signaling pathway in these cells is involved in the occurrence and development of AR. This result also implies an enhanced expression of deoxyribonucleic acid methyltransferases (DNMTs). To verify the relationship between ERK signaling and DNMT expression, AR mice were treated with PD98059, a specific inhibitor of the ERK1/2 signaling pathway. The results revealed that perturbations in ERK signaling were significantly positively correlated with the downregulation of DNMT1 expression. Pharmacological intervention is key to treating AR. This study demonstrated that Xingbi gel intervention affected both serum IgE levels and AR behavior scores in mice. Based on its effects on IFN-γ gene expression, the regulation of Th1/Th2 balance, and the ERK signaling pathway, research on the effects of Xingbi gel on AR may provide new avenues in its prevention and treatment.

摘要

变应性鼻炎(AR)是一种常见的非感染性慢性鼻黏膜疾病,主要由变应原暴露后免疫球蛋白E(IgE)介导。目前,关于AR的研究主要集中在细胞因子、IgE及其受体、嗜碱性粒细胞、嗜酸性粒细胞、肥大细胞和相关基因。其中,辅助性T(Th)1细胞和Th2细胞之间的失衡被认为是AR发病机制的重要基础。AR中最重要的细胞因子是分别由Th2细胞和Th1细胞分泌的白细胞介素(Il)-4和干扰素γ(IFN-γ)。Il-4和IFN-γ在调节IgE合成方面相互拮抗。在本研究中,AR小鼠4+ T细胞群中细胞外信号调节蛋白激酶(ERK)1/2的表达及其从p-ERK1/2的磷酸化显著增加,表明这些细胞中的ERK信号通路参与了AR的发生和发展。该结果还意味着DNA甲基转移酶(DNMTs)的表达增强。为了验证ERK信号与DNMT表达之间的关系,用ERK1/2信号通路的特异性抑制剂PD98059处理AR小鼠。结果显示,ERK信号的扰动与DNMT1表达的下调显著正相关。药物干预是治疗AR的关键。本研究表明,辛荜凝胶干预影响了小鼠的血清IgE水平和AR行为评分。基于其对IFN-γ基因表达、Th1/Th2平衡的调节以及ERK信号通路的影响,辛荜凝胶对AR作用的研究可能为其预防和治疗提供新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba5e/7917250/e40e5084e787/fsurg-07-619053-g0001.jpg

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