Kwon Oh Seong, Hwang Kyu-Taek, Choi Won Seok, Lee Ji-Yun
Department of Pathophysiology, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Biomol Ther (Seoul). 2025 Jul 1;33(4):692-703. doi: 10.4062/biomolther.2024.167. Epub 2025 Jun 10.
Asthma is an allergic inflammatory disease of the lungs characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). Exposure to environmental endotoxins, such as lipopolysaccharide (LPS), can exacerbate asthma severity. Phosphodiesterase (PDE) inactivates cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate, thereby aggravating inflammation. Accordingly, PDE inhibitors could be used to treat asthma. Herein, we studied the effects of BRL-50481 (BRL), a PDE7 inhibitor, in a murine model of ovalbumin (OVA)-induced allergic asthma with co-exposure to LPS. Mice were sensitized, challenged with OVA, and subsequently exposed to LPS. Mice were administered with BRL prior to the OVA challenge. We observed that BRL treatment could suppress hallmark features of asthma, including mediators of eosinophilic and neutrophilic inflammation, such as expression of antigen-specific immunoglobulin (Ig) E, interleukin (IL)-13, IL-6, and mucus hypersecretion. Mice co-exposed to OVA and LPS exhibited marked AHR, which was improved in BRL-treated mice because of inhibition of mucus overproduction. In conclusion, given that PDE7 inhibitors can regulate allergic inflammatory responses, these agents could be potential candidates for treating asthma.
哮喘是一种肺部过敏性炎症性疾病，其特征为嗜酸性粒细胞炎症、黏液分泌过多和气道高反应性（AHR）。接触环境内毒素，如脂多糖（LPS），可加重哮喘的严重程度。磷酸二酯酶（PDE）可使环磷酸腺苷和环磷酸鸟苷失活，从而加重炎症。因此，PDE抑制剂可用于治疗哮喘。在此，我们研究了PDE7抑制剂BRL-50481（BRL）在卵清蛋白（OVA）诱导的过敏性哮喘小鼠模型中同时接触LPS时的作用。小鼠经致敏、OVA激发，随后接触LPS。在OVA激发前给小鼠施用BRL。我们观察到，BRL治疗可抑制哮喘的标志性特征，包括嗜酸性粒细胞和中性粒细胞炎症介质，如抗原特异性免疫球蛋白（Ig）E、白细胞介素（IL）-13、IL-6的表达以及黏液分泌过多。同时接触OVA和LPS的小鼠表现出明显的AHR，而BRL治疗的小鼠由于黏液过度产生受到抑制，AHR得到改善。总之，鉴于PDE7抑制剂可调节过敏性炎症反应，这些药物可能是治疗哮喘的潜在候选药物。
