Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Republic of Korea.
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea.
Can Respir J. 2021 Mar 15;2021:8896108. doi: 10.1155/2021/8896108. eCollection 2021.
Quinoline-3-carboxamides have been used to treat autoimmune/inflammatory diseases in humans because they inhibit the functions of S100 calcium-binding protein A9 (S100A9), which participates in the development of neutrophilic inflammation in asthmatics and in an animal model of neutrophilic asthma. However, the therapeutic effects of these chemicals have not been evaluated in asthma. The purpose of this study was to evaluate the effect of paquinimod, one of the quinoline-3-carboxamides, on a murine model of neutrophilic asthma.
Paquinimod was orally administered to 6-week-old C57BL/6 mice sensitized and challenged with ovalbumin (OVA)/complete Freund's adjuvant (CFA) and OVA. Lung inflammation and remodeling were evaluated using bronchoalveolar lavage (BAL) and histologic findings including goblet cell count. S100A9, caspase-1, IL-1, MPO, IL-17, IFN-, and TNF- were measured in lung lysates using western blotting.
Paquinimod restored the enhancement of airway resistance and the increases in numbers of neutrophils and macrophages of BAL fluids and those of goblet cells in OVA/CFA mice toward the levels of sham-treated mice in a dose-dependent manner (0.1, 1, 10, and 25 mg/kg/day, p.o.). Concomitantly, p20 activated caspase-1, IL-1, IL-17, TNF-, and IFN- levels were markedly attenuated.
These data indicate that paquinimod effectively inhibits neutrophilic inflammation and remodeling in the murine model of neutrophilic asthma, possibly via downregulation of IL-17, IFN-, and IL-1.
喹啉-3-甲酰胺已被用于治疗人类的自身免疫/炎症性疾病，因为它们可以抑制 S100 钙结合蛋白 A9（S100A9）的功能，S100A9 参与了哮喘患者中性粒细胞炎症的发展以及中性粒细胞性哮喘的动物模型。然而，这些化学物质在哮喘中的治疗效果尚未得到评估。本研究的目的是评估喹啉-3-甲酰胺之一的帕奎莫德对中性粒细胞性哮喘小鼠模型的影响。
用卵清蛋白（OVA）/完全弗氏佐剂（CFA）和 OVA 致敏和激发 6 周龄 C57BL/6 小鼠后，口服给予帕奎莫德。通过支气管肺泡灌洗（BAL）和包括杯状细胞计数在内的组织学发现评估肺炎症和重塑。使用 Western blot 法在肺裂解物中测量 S100A9、半胱天冬酶-1、IL-1、MPO、IL-17、IFN-和 TNF-。
帕奎莫德以剂量依赖性方式（0.1、1、10 和 25mg/kg/天，口服）恢复了 OVA/CFA 小鼠气道阻力的增强以及 BAL 液中中性粒细胞和巨噬细胞数量以及杯状细胞数量的增加，使其向假手术处理的小鼠水平恢复（p<0.05）。同时，p20 激活的半胱天冬酶-1、IL-1、IL-17、TNF-和 IFN-水平显著降低。
这些数据表明，帕奎莫德可有效抑制中性粒细胞性哮喘小鼠模型中的中性粒细胞炎症和重塑，可能是通过下调 IL-17、IFN-和 IL-1 实现的。
