State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Biochem Pharmacol. 2018 Aug;154:18-27. doi: 10.1016/j.bcp.2018.04.006. Epub 2018 Apr 13.
Autoimmune uveitis is a sight-threatening ocular inflammatory disorder. Immunological inflammation is regarded as the key to pathogenesis in autoimmune uveitis. Baicalin, the major bioactive component of Scutellaria baicalensis, possesses immunomodulatory properties. However, the role of baicalin in uveitis and its underlying mechanisms remain unclear. In the current study, we found that baicalin treatment obviously inhibited the intraocular inflammatory process in mice with experimental autoimmune uveitis, along with clear declines in infiltrated inflammatory cells and inflammatory cytokine transcription in the retina and draining lymph nodes. Furthermore, baicalin treatment increased the frequency and number of regulatory T cells and decreased the frequency and number of effector T cells (Th1 and Th17 cells) in the draining lymph nodes of mice with experimental autoimmune uveitis. In vitro, baicalin treatment suppressed interphotoreceptor retinoid binding protein-specific CD4+ T cell proliferation and converted CD4+ T cell differentiation. Furthermore, the expression of aryl hydrocarbon receptor was activated by baicalin treatment. Baicalin-mediated modulation of CD4+ T cell differentiation was partially abrogated by the suppression of aryl hydrocarbon receptor. These findings suggest that baicalin modulates the Treg/Teff balance and CD4+ T cell proliferation to ameliorate experimental autoimmune uveitis by activating the aryl hydrocarbon receptor.
自身免疫性葡萄膜炎是一种威胁视力的眼内炎症性疾病。免疫炎症被认为是自身免疫性葡萄膜炎发病机制的关键。黄芩苷是黄芩的主要生物活性成分，具有免疫调节作用。然而，黄芩苷在葡萄膜炎中的作用及其潜在机制尚不清楚。在本研究中，我们发现黄芩苷治疗明显抑制了实验性自身免疫性葡萄膜炎小鼠的眼内炎症过程，同时视网膜和引流淋巴结中的浸润性炎症细胞和炎症细胞因子转录明显下降。此外，黄芩苷治疗增加了实验性自身免疫性葡萄膜炎小鼠引流淋巴结中调节性 T 细胞的频率和数量，减少了效应 T 细胞（Th1 和 Th17 细胞）的频率和数量。体外，黄芩苷治疗抑制了感光细胞间视黄醇结合蛋白特异性 CD4+T 细胞的增殖，并转化了 CD4+T 细胞的分化。此外，黄芩苷处理激活了芳香烃受体的表达。通过抑制芳香烃受体，黄芩苷介导的 CD4+T 细胞分化的调节部分被阻断。这些发现表明，黄芩苷通过激活芳香烃受体调节 Treg/Teff 平衡和 CD4+T 细胞增殖，从而改善实验性自身免疫性葡萄膜炎。
