IL-31/TRPV1 通路介导 OVA 致敏 Balb/c 小鼠因皮肤接触 DINP 而加剧的过敏性哮喘
2024/02/23
摘要
背景：已经有人提出，皮肤接触邻苯二甲酸二异壬酯（DINP）可能作为过敏性炎症和哮喘的佐剂。然而，目前的发现并没有提供足够的证据来支持这一主张。
目的：本研究旨在探讨皮肤接触 DINP 对过敏性哮喘加重的影响和机制。
方法：采用OVA致敏小鼠进行了本研究。评估了肺组织病理学和气道高反应性（AHR）。测量了免疫球蛋白（总IgE，OVA-IgE和OVA-IgG1）、细胞因子（IL-31，IL-4，IL-5，IL-6，IL-13和INF-γ）以及TRPV1的表达水平。为了研究皮肤接触DINP导致变应性哮喘加重的机制，进行了使用IL-31拮抗剂SB-431542和TRPV1拮抗剂辣椒碱（CZP）的阻断分析。
结果：研究结果显示，DINP和OVA同时暴露导致吸气阻力（Ri）和呼气阻力（Re）增加，肺动态顺应性（Cldyn）最小值减少，并且气道重塑加重。此外，发现这种暴露导致IL-31和TRPV1水平增加，它们是Th2细胞因子（IL-4、IL-5、IL-6和IL-13）以及免疫球蛋白（总IgE、OVA-IgE和OVA-IgG1）的生物标志物，同时降低了Th1细胞因子（IFN-γ）的生物标志物。然而，这些损害在SB-431542或CZP给药后显示出改善。
结论：本研究的结果表明，IL-31/TRPV1途径在皮肤接触DINP加重的OVA诱导的过敏性哮喘中起着调节作用。
The IL-31/TRPV1 pathway mediates allergic asthma exacerbated by DINP dermal exposure in OVA-sensitized Balb/c mice
Peng Q, Wu Y, Li Y, Lu C, Yao R, Hu S, Ma N, Chen S, Yang X, Ma P
Abstract
Background:The potential role of dermal exposure diisononyl phthalate (DINP) as an adjuvant in allergic inflammation and asthma has been suggested. However, the current findings do not provide enough evidence to support this claim.
Objective:The purpose of this investigation was to examine the impact and mechanisms of allergic asthma exacerbation through the dermal exposure to DINP.
Methods:The study was undertaken using OVA-sensitized mice. Lung histopathology and airway hyperreactivity (AHR) were assessed. Expression levels of immunoglobulins (t-IgE, OVA-IgE and OVA-IgG1), cytokines (IL-31, IL-4, IL-5, IL-6, IL-13 and INF-γ), and TRPV1 were measured. To investigate the mechanism by which allergic asthma worsens due to dermal exposure to DINP, the blockade analysis using the IL-31 antagonist SB-431542 and the TRPV1 antagonist capsazepine (CZP) were performed.
Results:The findings of the study revealed that the simultaneous exposure to DINP and OVA resulted in an increase in inspiratory resistance (Ri) and expiratory resistance (Re), a decrease in the minimum value of lung dynamic compliance (Cldyn), and worsened airway remodeling. Additionally, it was found that this exposure led to an increase in the levels of IL-31 and TRPV1, which are biomarkers of Th2 cytokines (IL-4, IL-5, IL-6, and IL-13), as well as immunoglobulins (Total IgE, OVA-lgE, and OVA-IgG1), while decreasing the biomarker of Th1 cytokines (IFN-γ). However, these impairments showed improvement after the administration of SB-431542 or CZP.
Conclusion:The findings of this research indicate that the IL-31/TRPV1 pathway plays a moderating function in OVA-induced allergic asthma worsened by dermal exposure to DINP.
背景：已经有人提出，皮肤接触邻苯二甲酸二异壬酯（DINP）可能作为过敏性炎症和哮喘的佐剂。然而，目前的发现并没有提供足够的证据来支持这一主张。
目的：本研究旨在探讨皮肤接触 DINP 对过敏性哮喘加重的影响和机制。
方法：采用OVA致敏小鼠进行了本研究。评估了肺组织病理学和气道高反应性（AHR）。测量了免疫球蛋白（总IgE，OVA-IgE和OVA-IgG1）、细胞因子（IL-31，IL-4，IL-5，IL-6，IL-13和INF-γ）以及TRPV1的表达水平。为了研究皮肤接触DINP导致变应性哮喘加重的机制，进行了使用IL-31拮抗剂SB-431542和TRPV1拮抗剂辣椒碱（CZP）的阻断分析。
结果：研究结果显示，DINP和OVA同时暴露导致吸气阻力（Ri）和呼气阻力（Re）增加，肺动态顺应性（Cldyn）最小值减少，并且气道重塑加重。此外，发现这种暴露导致IL-31和TRPV1水平增加，它们是Th2细胞因子（IL-4、IL-5、IL-6和IL-13）以及免疫球蛋白（总IgE、OVA-IgE和OVA-IgG1）的生物标志物，同时降低了Th1细胞因子（IFN-γ）的生物标志物。然而，这些损害在SB-431542或CZP给药后显示出改善。
结论：本研究的结果表明，IL-31/TRPV1途径在皮肤接触DINP加重的OVA诱导的过敏性哮喘中起着调节作用。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(Sci Total Environ. 2024 Feb 20; DOI: 0.1016/j.scitotenv.2023.169613)
(Sci Total Environ. 2024 Feb 20; DOI: 0.1016/j.scitotenv.2023.169613)
The IL-31/TRPV1 pathway mediates allergic asthma exacerbated by DINP dermal exposure in OVA-sensitized Balb/c mice
Peng Q, Wu Y, Li Y, Lu C, Yao R, Hu S, Ma N, Chen S, Yang X, Ma P
Abstract
Background:The potential role of dermal exposure diisononyl phthalate (DINP) as an adjuvant in allergic inflammation and asthma has been suggested. However, the current findings do not provide enough evidence to support this claim.
Objective:The purpose of this investigation was to examine the impact and mechanisms of allergic asthma exacerbation through the dermal exposure to DINP.
Methods:The study was undertaken using OVA-sensitized mice. Lung histopathology and airway hyperreactivity (AHR) were assessed. Expression levels of immunoglobulins (t-IgE, OVA-IgE and OVA-IgG1), cytokines (IL-31, IL-4, IL-5, IL-6, IL-13 and INF-γ), and TRPV1 were measured. To investigate the mechanism by which allergic asthma worsens due to dermal exposure to DINP, the blockade analysis using the IL-31 antagonist SB-431542 and the TRPV1 antagonist capsazepine (CZP) were performed.
Results:The findings of the study revealed that the simultaneous exposure to DINP and OVA resulted in an increase in inspiratory resistance (Ri) and expiratory resistance (Re), a decrease in the minimum value of lung dynamic compliance (Cldyn), and worsened airway remodeling. Additionally, it was found that this exposure led to an increase in the levels of IL-31 and TRPV1, which are biomarkers of Th2 cytokines (IL-4, IL-5, IL-6, and IL-13), as well as immunoglobulins (Total IgE, OVA-lgE, and OVA-IgG1), while decreasing the biomarker of Th1 cytokines (IFN-γ). However, these impairments showed improvement after the administration of SB-431542 or CZP.
Conclusion:The findings of this research indicate that the IL-31/TRPV1 pathway plays a moderating function in OVA-induced allergic asthma worsened by dermal exposure to DINP.
上一篇：
Tectorigenin通过激活Th2介导的过敏性哮喘小鼠中的Keap1/Nrf2/HO-1信号通路来抑制氧化应激
下一篇：
阻断CD226调节ILC2功能并减轻气道高反应性
