Institute of Chinese Medicine, Guangzhou University of Chinese medicine, Guangzhou 510006, China.
Institute of Otorhinolaryngology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Int Immunopharmacol. 2018 Aug;61:241-248. doi: 10.1016/j.intimp.2018.06.011. Epub 2018 Jun 9.
The prevalence of allergic rhinitis has risen sharply. Previous work has demonstrated the anti-inflammatory effect of catechin, including in models of allergic disease. However, the molecular mechanisms underlying this therapeutic effect remain unclear. Thymic stromal lymphopoietin(TSLP), as a molecule from epithelial cell, has been identified that plays a significant role in the development of allergic disease, and the production of TSLP is related to activation of the NF-κB signaling pathway. For that, we try to research the treatment of catechin for allergic rhinitis and found out possible mechanism under this effect, which was based on TSLP factor.
Here, the anti-inflammatory effects of catechin were studied in an ovalbumin-induced allergic rhinitis murine model and a vitro experiments using poly(I:C)-stimulated human nasal epithelial cells(HNEpCs). The pharmacological effects of catechin in allergic rhinitis mice were assessed by observing the allergic symptoms, performing hematoxylin and eosin staining and Giemsa staining of the nasal tissues. Additionally, the TSLP expression in epithelial cells was tested by enzyme-linked immunosorbent assays, immunohistochemistry, and western blots. The serum levels of interleukin-5, interleukin-13, and ovalbumin-specific immunoglobulin-E were detected by enzyme-linked immunosorbent assays, and the balance between T helper type 1 and T helper type 2 cells was assessed by flow cytometry. The expression levels of phospho-NF-κBp65, IκBα, and NF-κBp65 proteins were further investigated by western blots or immunofluorescence.
Our results reveal that catechin, in doses of 75, 150, or 300 mg/kg, remitted the allergic symptoms in mice with allergic rhinitis, like sneezing and nasal rubbing. Catechin could reduce the levels of interleukin-5, interleukin-13, and ovalbumin-specific immunoglobulin-E in the serum and restored the T helper type 2/T helper type 1 cell balance and also had anti-thymic stromal lymphopoietin effects. Moreover, as an upstream regulator of TSLP, the NF-κB signal pathway was also suppressed after catechin treatment, which was demonstrated by the observed decrease in phospho-NF-κBp65 and NF-κBp65 levels and the reduction of IκBα degradation and NF-κBp65 nuclear translocation.
Catechin effectively reduced the inflammation in allergic rhinitis. The underlying mechanism is that catechin inhibited the expression of TSLP in epithelial cells by influencing NF-κB/TSLP pathway.
过敏性鼻炎的患病率急剧上升。先前的研究已经证实儿茶素具有抗炎作用，包括在过敏性疾病模型中。然而，这种治疗效果的分子机制尚不清楚。胸腺基质淋巴细胞生成素（TSLP）作为上皮细胞来源的一种分子，已被确定在过敏性疾病的发展中发挥重要作用，而 TSLP 的产生与 NF-κB 信号通路的激活有关。因此，我们尝试研究儿茶素治疗过敏性鼻炎的作用，并发现了可能的作用机制，该机制基于 TSLP 因子。
在这里，我们在卵清蛋白诱导的过敏性鼻炎小鼠模型和多聚（I：C）刺激的人鼻上皮细胞（HNEpCs）的体外实验中研究了儿茶素的抗炎作用。通过观察过敏症状、进行鼻组织的苏木精和伊红染色和吉姆萨染色，评估儿茶素在过敏性鼻炎小鼠中的药理作用。此外，通过酶联免疫吸附试验、免疫组织化学和蛋白质印迹法检测上皮细胞中的 TSLP 表达。通过酶联免疫吸附试验检测白细胞介素-5、白细胞介素-13 和卵清蛋白特异性免疫球蛋白-E 的血清水平，并通过流式细胞术评估辅助性 T 细胞 1 型和辅助性 T 细胞 2 型细胞之间的平衡。通过蛋白质印迹法或免疫荧光法进一步研究磷酸化 NF-κBp65、IκBα 和 NF-κBp65 蛋白的表达水平。
我们的结果表明，儿茶素以 75、150 或 300mg/kg 的剂量给药，可缓解过敏性鼻炎小鼠的过敏症状，如打喷嚏和鼻摩擦。儿茶素可以降低血清中白细胞介素-5、白细胞介素-13 和卵清蛋白特异性免疫球蛋白-E 的水平，并恢复辅助性 T 细胞 2 型/辅助性 T 细胞 1 型细胞平衡，同时具有抗胸腺基质淋巴细胞生成素作用。此外，作为 TSLP 的上游调节剂，NF-κB 信号通路也被儿茶素处理所抑制，这表现为磷酸化 NF-κBp65 和 NF-κBp65 水平的降低，以及 IκBα 降解和 NF-κBp65 核转位的减少。
儿茶素可有效减轻过敏性鼻炎的炎症。其作用机制是通过影响 NF-κB/TSLP 通路抑制上皮细胞中 TSLP 的表达。
