调节喘-COPD重叠反应与IL-17抑制的反应
Leandro do Nascimento Camargo1,2, Renato Fraga Righetti1,2, Francine Maria de Almeida1
1Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil.
Frontiers in immunology
|November 15, 2023
概括
在喘-COPD重叠 (ACO) 的小鼠模型中,抑制介素-17 (IL-17) 降低了呼吸道过敏反应和炎症. 这种治疗还调节了细胞因子的产生,细胞外矩阵的重塑和肺部的氧化应激.
科学领域:
- 肺部医学 肺部医学
- 免疫学 免疫学 免疫学
- 呼吸系统研究 呼吸系统研究
背景情况:
- 干白素-17 (IL-17) 是喘和COPD中炎症和肺重塑的关键调解剂.
- 由于这两种疾病的综合病理,喘-COPD重叠 (ACO) 带来了独特的挑战.
- 了解IL-17在ACO中的作用对于开发向疗法至关重要.
研究的目的:
- 在ACO的小鼠模型中研究抗IL-17单克隆抗体治疗的治疗效果.
- 评估IL-17抑制对空气道过敏反应,炎症和肺重塑在ACO中的影响.
- 探索在ACO中通过抗IL-17疗法调节特定的信号通路和生物标志物.
主要方法:
- 使用卵蛋白 (OVA) 和猪胰腺弹性酶 (PPE) 敏感化建立了一个ACO小鼠模型.
- 小鼠接受了抗IL-17单克隆抗体或盐水对照剂的治疗.
- 评估了气道过敏反应,支气管洗液 (BALF) 细胞计数,以及炎症,重塑,氧化应激和信号通路的肺组织标志物.
主要成果:
- 在ACO小鼠中,抗IL-17治疗显著降低了气道过敏反应 (Rrs, Ers, Raw, Gtis).
- 治疗导致BALF.的炎症细胞数量 (中性粒细胞,巨细胞) 减少.
- 抑制IL-17减弱了各种细胞因子 (IL-1β,IL-6,IL-13,IL-17,IL-33),矩阵金属蛋白酶 (MMP-9,MMP-12),TGF-β, I型原蛋白,iNOS,以及氧化应激标志物 (8-iso-PGF2α).
- 包括NF-kB,ROCK-1和ROCK-2在内的信号通路也因抗IL-17治疗而减弱.
结论:
- 在ACO小鼠模型中,抑制IL-17有效调节气道炎症和高反应性.
- 抗IL-17疗法通过减少细胞因子的产生,细胞外基质重塑和氧化应激来影响肺组织.
- 这些发现表明,向IL-17,可能通过调节NF-kB和FOXP3通路,是ACO的一种有前途的治疗策略.
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