The effects of resiquimod in an ovalbumin-induced allergic rhinitis model
The effects of resiquimod in an ovalbumin-induced allergic rhinitis model
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瑞西莫德在卵清蛋白诱导的过敏性鼻炎模型中的作用
DOI：
10.1016/j.intimp.2018.04.015
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发表时间：
2018
影响因子：
5.6
通讯作者：
Qin TJ
中科院分区：
文献类型：
--
作者：
Qu Shenhong;Qin Taijie;Li Min;Zhang Shaojie;Ye Linsong;Wei Jiazhang;Fan Hua;Chen Baiwen;Qin Taijie;Qin TJ
越来越多的证据表明，Toll样受体7/8（TLR 7/8）激动剂瑞喹莫特（R848）是一种潜在的2型免疫抑制剂。然而，介导其治疗效果的机制尚未完全了解。本研究观察了R848对OVA诱导的小鼠变应性鼻炎（AR）的影响及对IL-25、IL-33、TSLP、T细胞免疫球蛋白粘蛋白1（TIM 1）和T细胞免疫球蛋白粘蛋白3（TIM 3）表达的影响。BALB/c小鼠鼻内致敏，并用卵清蛋白（OVA）攻击，和R848腹腔注射到AR小鼠。采用苏木精-伊红（H & E）和过碘酸-希夫（PAS）染色观察鼻黏膜组织学变化，酶联免疫吸附试验（ELISA）检测血清细胞因子水平，实时定量RT-PCR（qRT-PCR）检测脾脏IFN-γ、IL-17和Foxp 3 mRNA表达水平，免疫组化法检测血清IL-17和Foxp 3 mRNA表达水平。采用流式细胞术检测小鼠脾脏中Th 1、Th 2、Th 17、Treg和TIM 3 + IFN-γ + Th 1细胞比例，免疫荧光染色检测鼻黏膜中TIM 1、TIM 3和IL-33表达水平。结果表明，模型组大鼠鼻黏膜嗜酸性粒细胞浸润减少，杯状细胞增生减少，血清IL-13、IL-17、IL-25和IL-33水平降低，脾脏IFN-γ和Foxp 3的相对mRNA表达上调，IL-17的相对mRNA表达下调;降低OVA诱导的AR小鼠脾脏中Th 2、Th 17和TIM 3 + IFN-γ + Th 1细胞比例，增加Th 1和Treg细胞比例，抑制鼻粘膜中TIM 1和TIM 3的表达，但增加IL-33的表达。R848抑制IL-25、IL-33的释放和TIM 1、TIM 3的表达，可能是其抗过敏作用的机制之一。
Growing evidence indicates that the Toll-like receptor7/8(TLR7/8) agonist resiquimod (R848) is a potential inhibitor of type-2 immunity. However, the mechanisms mediating its therapeutic effects are not fully understood. This study investigated the effects of R848 on OVA-induced allergic rhinitis(AR) mice and the expression of IL-25, IL-33, TSLP, T-cell immunoglobulin mucin1 (TIM1) and T-cell immunoglobulin mucin3 (TIM3). BALB/c mice were intranasally sensitized and challenged with ovalbumin (OVA), and R848 was intraperitoneally injected into AR mice. Histological changes in the nasal mucosa were evaluated by hematoxylin and eosin (H & E) and Periodic Acid-Schiff (PAS) staining; cytokine levels in serum were measured with enzyme-linked immunosorbent assays (ELISAs);the mRNA expression levels of IFN-γ, IL-17 and Foxp3 in the spleen determined by quantitative real-time RT-PCR (qRT-PCR); the proportions of Th1, Th2, Th17, Treg and TIM3 + IFN-γ + Th1 cells in the spleen were assessed with flow cytometry; TIM1, TIM3 and IL-33 expression levels in the nasal mucosa were evaluated with immunofluorescence staining(IF).R848 alleviated the nasal allergic symptoms; reduced eosinophil cell infiltration, goblet cell hyperplasia in the nasal mucosa; reduced IL-13, IL-17, IL-25 and IL-33 levels in serum; upregulated the relative mRNA expression of IFN-γ and Foxp3, and downregulated the relative mRNA expression of IL-17 in the spleen; decreased Th2, Th17 and TIM3 + IFN-γ + Th1 cells ratios, increased the proportion of Th1 and Treg cells in the spleen; suppressed TIM1 and TIM3,but increased IL-33 expression in the nasal mucosa in OVA-induced AR mice. R848 suppresses IL-25, IL-33 released and TIM1, TIM3 expression, which may contribute to its anti-allergic effects.