College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
Pathophysiology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
Arch Pharm Res. 2022 Jan;45(1):51-62. doi: 10.1007/s12272-021-01367-x. Epub 2022 Jan 4.
Asian sand dust (ASD), which mainly originates in China and Mongolia in the spring and blows into Korea, can exacerbate respiratory and immunological diseases. This study aims to observe effects of co-exposure to ASD on ovalbumin (OVA)-induced asthmatic lung inflammation and of treatment with a phosphodiesterase 7 (PDE7) inhibitor in a mouse model. The challenge with OVA increased airway hyperresponsiveness (AHR) and inflammatory cell infiltration into the lung tissue. Interleukin (IL)-13, tumor necrosis factor-alpha, monocyte-protein-1, mucin, and antigen-specific IgE and IgG1 production increased in mouse serum. The co-exposure of ASD significantly exacerbated these effects in this asthma model. Notably, the administration of a PDE7 inhibitor, BRL-50481 (BRL), significantly reduced AHR, infiltration of inflammatory cells into the lungs, and the levels of type 2 T helper cell-related cytokines, antigen-specific immunoglobulins, and mucin. Thus, the administration of BRL ameliorated OVA-induced allergic asthmatic responses exacerbated by co-exposure to ASD. This study suggests that PDE7 inhibition can be a therapeutic strategy for inflammatory lung diseases and asthma via the regulation of T lymphocytes and reduction of IL-13, and, consequently, mucin production.
亚洲沙尘（ASD）主要在春季源自中国和蒙古国，并吹入韩国，可使呼吸道和免疫性疾病恶化。本研究旨在观察共暴露于 ASD 对卵清蛋白（OVA）诱导的哮喘性肺炎症的影响，以及磷酸二酯酶 7（PDE7）抑制剂在小鼠模型中的治疗效果。OVA 激发增加气道高反应性（AHR）和炎性细胞浸润到肺组织。白细胞介素（IL）-13、肿瘤坏死因子-α、单核细胞蛋白-1、粘蛋白和抗原特异性 IgE 和 IgG1 在小鼠血清中的产生增加。ASD 的共暴露在该哮喘模型中显著加重了这些作用。值得注意的是，PDE7 抑制剂 BRL-50481（BRL）的给药显著降低了 AHR、肺内炎症细胞浸润以及 2 型 T 辅助细胞相关细胞因子、抗原特异性免疫球蛋白和粘蛋白的水平。因此，BRL 的给药通过调节 T 淋巴细胞和减少白细胞介素 13，从而减轻了共暴露于 ASD 加重的 OVA 诱导的过敏性哮喘反应。本研究表明，PDE7 抑制可通过调节 T 淋巴细胞和减少白细胞介素 13 以及减少粘蛋白的产生，成为治疗炎症性肺疾病和哮喘的一种治疗策略。
