Shandong University of Traditional Chinese Medicine, Jinan 250002, China.
The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250002, China.
Int Immunopharmacol. 2023 Mar;116:109809. doi: 10.1016/j.intimp.2023.109809. Epub 2023 Feb 6.
Uveitis is an immune eye disease that can seriously impair vision. Glucocorticoids (GC) have been extensively used to treat uveitis, though the mechanisms have not been fully elucidated. In this study, we investigated the regulatory effects of prednisone acetate (PA) on the Th1/Th2 and Th17/Treg balance in experimental autoimmune uveitis (EAU) through modulating the Notch signaling pathway. Briefly, Lewis rats were randomly divided into the normal control (NC), EAU, and EAU + PA groups. Rats in EAU and EAU + PA groups were induced EAU, while those in the EAU + PA group were treated with PA. Clinical and histopathological scores were employed to assess the progression of EAU. The expression levels of Notch signaling-related molecules (Notch1, Notch2, Dll3, Dll4, and Rbpj) and Th-associated cytokines (IFN-γ, IL-4, IL-10, and IL-17) were assessed via quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the frequencies of Th1, Th2, Th17 and Treg cells were detected by flow cytometry. These experimental results indicated that activation of the Notch signaling pathway occurred in EAU rats and resulted in a severe imbalance of the Th17/Treg and Th1/Th2 ratios. PA treatment significantly alleviated ocular inflammation, inhibited activation of the Notch signaling pathway, and declined Th1, and Th17 cell differentiation, thereby restoring the Th1/Th2 and Th17/Treg balance. Collectively, PA can positively enhance the systemic immune response and improve the intraocular microenvironmental homeostasis by inhibiting activation of the Notch signaling pathway and by restoring Th1/Th2 and Th17/Treg balance, thus achieving the goal of treating uveitis.
葡萄膜炎是一种免疫性眼病，可严重损害视力。糖皮质激素（GC）已广泛用于治疗葡萄膜炎，但作用机制尚未完全阐明。在这项研究中，我们通过调节 Notch 信号通路，研究了醋酸泼尼松龙（PA）对实验性自身免疫性葡萄膜炎（EAU）中 Th1/Th2 和 Th17/Treg 平衡的调节作用。简要地说，将 Lewis 大鼠随机分为正常对照组（NC）、EAU 组和 EAU+PA 组。EAU 组和 EAU+PA 组大鼠诱导 EAU，而 EAU+PA 组大鼠用 PA 治疗。临床和组织病理学评分用于评估 EAU 的进展。通过定量 PCR（qPCR）和酶联免疫吸附试验（ELISA）评估 Notch 信号相关分子（Notch1、Notch2、Dll3、Dll4 和 Rbpj）和 Th 相关细胞因子（IFN-γ、IL-4、IL-10 和 IL-17）的表达水平。此外，通过流式细胞术检测 Th1、Th2、Th17 和 Treg 细胞的频率。这些实验结果表明，EAU 大鼠 Notch 信号通路被激活，导致 Th17/Treg 和 Th1/Th2 比值严重失衡。PA 治疗显著减轻眼部炎症，抑制 Notch 信号通路的激活，减少 Th1 和 Th17 细胞分化，从而恢复 Th1/Th2 和 Th17/Treg 平衡。总之，PA 通过抑制 Notch 信号通路的激活和恢复 Th1/Th2 和 Th17/Treg 平衡，积极增强全身免疫反应，改善眼内微环境的稳态，从而达到治疗葡萄膜炎的目的。
