Anti-allergic rhinitis activity of α-lipoic acid via balancing Th17/Treg expression and enhancing Nrf2/HO-1 pathway signaling
Anti-allergic rhinitis activity of α-lipoic acid via balancing Th17/Treg expression and enhancing Nrf2/HO-1 pathway signaling
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DOI：
10.1038/s41598-020-69234-1
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发表时间：
2020-07-27
影响因子：
4.6
通讯作者：
Chai, Ok Hee
中科院分区：
文献类型：
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作者：
Thi Van Nguyen;Piao, Chun Hua;Chai, Ok Hee
建立卵清蛋白（OVA）诱导的过敏性鼻炎（AR）小鼠模型，以研究α-硫辛酸（LA）是否对上呼吸道炎症具有保护作用。 BALB/c小鼠通过腹腔注射致敏并通过鼻内应用OVA进行攻击。在 OVA 攻击前 1 小时，小鼠每天一次口服不同剂量的 LA（2、10、50 mg/kg）和地塞米松（Dex；2.5 mg/kg）。测量过敏性鼻症状、OVA 特异性免疫球蛋白、细胞因子和转录因子的水平。评估鼻和肺的组织病理学。 LA 给药显着减轻了鼻部症状，如摩擦和打喷嚏，显着降低了血清 OVA 特异性 IgE 和 IgG1 水平。 LA治疗组的Treg细胞因子IL-10和Treg转录因子Foxp3水平显着上调。相比之下，Th17 细胞因子 IL-17 和 Th17 转录因子 STAT3 以及 ROR gamma 的水平下调。 LA 极大增强了核因子红细胞源性 2/血红素加氧酶 1 (Nrf2/HO-1) 通路信号传导，抑制 NF-kappa B/I kappa B 的激活，显着抑制促炎细胞因子 TNF-α、IL-1β、IL-6、IL-8 和趋化因子 COX-2 的水平。 LA 有效改善了 AR 小鼠鼻腔和肺组织的组织学改变。基于这些结果，我们认为 LA 因其在控制 Th17/Treg 平衡和增强 Nrf2/HO-1 通路信号传导方面的作用而可能成为 OVA 诱导的 AR 的潜在治疗剂。
An ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model was established to investigate whether alpha -Lipoic acid (LA) has a protective effect against upper respiratory tract inflammation. BALB/c mice were sensitized by intraperitoneal injection and challenged by intranasal application of OVA. Mice were orally administered various doses of LA once daily (2, 10, 50 mg/kg) and dexamethasone (Dex; 2.5 mg/kg) 1 h before OVA challenge. Allergic nasal symptoms, levels of OVA-specific immunoglobulins, cytokines, and transcription factors were measured. Nasal and lung histopathology were evaluated. LA administration significantly alleviated the nasal symptoms such as rubbing and sneezing, markedly reduced both serum OVA-specific IgE and IgG1 levels. The LA treatment group showed markedly up-regulated levels of the Treg cytokine IL-10 and Treg transcription factor Foxp3. In contrast, it showed down-regulated levels of the Th17 cytokine IL-17 and the Th17 transcription factor STAT3, and ROR gamma. LA greatly enhanced the nuclear factor erythroid-derived 2/heme oxygenase 1 (Nrf2/HO-1) pathway signaling and inhibited the activation of NF-kappa B/I kappa B, markedly suppressed the levels of pro-inflammatory cytokines TNF-alpha, IL-1 beta, IL-6, IL-8 and chemokine COX-2. The histologic alterations of nasal and lung tissues of AR mice were effectively ameliorated by LA. Based on these results, we suggest that LA could be a potential therapeutic agent in OVA-induced AR by virtue of its role in controlling the Th17/Treg balance and enhancing Nrf2/HO-1 pathway signaling.