Yang Qingqing, Kong Lingwen, Huang Weiling, Mohammadtursun Nabijan, Li Xiumin, Wang Guifang, Wang Lixin
Department of Respiratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, P.R. China.
Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Int J Mol Med. 2020 Oct;46(4):1389-1398. doi: 10.3892/ijmm.2020.4682. Epub 2020 Jul 22.
Asthma is a common chronic inflammatory airway disease. Recent studies have reported that interleukin (IL)‑33 is a potential link between the airway epithelium and Th2‑type inflammatory responses, which are closely related to the progression of asthma. The IL‑33 receptor, ST2, is highly expressed in group 2 innate lymphoid cells (ILC2s), Th2 cells, mast cells, eosinophils and natural killer (NK) cells. Cnidii Fructus is a Chinese herb with a long history of use in the treatment of asthma in China. Osthole is one of the major components of Cnidii Fructus. The present study examined the anti‑asthmatic effects of osthole in mice and aimed to elucidate the underlying mechanisms involving the IL‑33/ST2 pathway. BALB/c mice were sensitized and challenged with ovalbumin and then treated with an intraperitoneal injection of osthole (25 and 50 mg/kg). Subsequently, the airway hyper‑responsiveness (AHR) and inflammation of the lungs were evaluated. The amounts of IL‑4, IL‑5, IL‑13, interferon (IFN)‑γ and IL‑33 in the bronchoalveolar lavage fluid (BALF) were measured by Luminex assay and their mRNA levels in the lungs were measured by reverse transcription‑quantitative PCR. The histopathology of the lungs was performed with H&E, PAS and Masson's staining. The expression of ST2 in the lungs was evaluated by immunohistochemistry. The data demonstrated that osthole markedly reduced AHR and decreased the number of eosinophils and lymphocytes in BALF. It was also observed that osthole significantly inhibited the release of Th2‑type cytokines (IL‑4, IL‑5 and IL‑13) and upregulated the IFN‑γ level in BALF. Moreover, osthole significantly attenuated the IL‑33 and ST2 expression in the lungs of asthmatic mice. On the whole, osthole attenuated ovalbumin‑induced lung inflammation through the inhibition of IL‑33/ST2 signaling in an asthmatic mouse model. These results suggest that osthole is a promising target for the development of an asthma medication.
哮喘是一种常见的慢性炎症性气道疾病。最近的研究报道，白细胞介素（IL）-33是气道上皮与2型炎症反应之间的潜在联系，而2型炎症反应与哮喘的进展密切相关。IL-33受体ST2在2型固有淋巴细胞（ILC2s）、Th2细胞、肥大细胞、嗜酸性粒细胞和自然杀伤（NK）细胞中高表达。蛇床子是一种在中国有着悠久治疗哮喘历史的中药。蛇床子素是蛇床子的主要成分之一。本研究检测了蛇床子素对小鼠的抗哮喘作用，并旨在阐明其涉及IL-33/ST2通路的潜在机制。用卵清蛋白对BALB/c小鼠进行致敏和激发，然后腹腔注射蛇床子素（25和50mg/kg）进行治疗。随后，评估气道高反应性（AHR）和肺部炎症。通过Luminex检测法测定支气管肺泡灌洗液（BALF）中IL-4、IL-5、IL-13、干扰素（IFN）-γ和IL-33的含量，并通过逆转录定量PCR测定其在肺中的mRNA水平。用苏木精-伊红（H&E）、Periodic acid-Schiff（PAS）和Masson染色进行肺组织病理学检查。通过免疫组织化学评估肺中ST2的表达。数据表明，蛇床子素显著降低AHR，并减少BALF中嗜酸性粒细胞和淋巴细胞的数量。还观察到蛇床子素显著抑制2型细胞因子（IL-4、IL-5和IL-13）的释放，并上调BALF中IFN-γ水平。此外，蛇床子素显著减弱哮喘小鼠肺中IL-33和ST2的表达。总体而言，在哮喘小鼠模型中，蛇床子素通过抑制IL-33/ST2信号传导减轻卵清蛋白诱导的肺部炎症。这些结果表明，蛇床子素是一种有前景的哮喘治疗药物开发靶点。
