Liu Yuhuan, Jin Lianhua, Peng Li, Sun Meihua
Department of Pediatric Respiration, Children's Medical Center, The First Hospital of Jilin University, Changchun, 130021, PR China.
Department of Pediatric Cardiovascular, Children's Medical Center, The First Hospital of Jilin University, Changchun, 130021, PR China.
Arch Biochem Biophys. 2025 Sep;771:110502. doi: 10.1016/j.abb.2025.110502. Epub 2025 Jun 9.
In the context of asthma pathophysiology, especially during exacerbations and airway inflammation, interleukin-33 (IL-33) holds a pivotal role. This study delves into elucidating the impact of IL-33 on ferroptosis during asthma exacerbations. Through comprehensive transcriptomic and proteomic analyses, IL-33 and GPX4 emerged as crucial regulators in this intricate process. In vitro experiments showcased the remarkable anti-inflammatory and ferroptosis-mitigating effects of an IL-33 antibody in IL-13-induced BEAS-2B cells. Subsequent in vivo validation in mice underscored the ability of the IL-33 antibody to diminish inflammatory responses, enhance GPX4 expression, and ameliorate asthma symptoms. These compelling findings suggest that the IL-33 antibody holds promise in suppressing ferroptosis, alleviating inflammation, and modulating GPX4 expression, thereby proposing novel therapeutic strategies for managing asthma exacerbations by targeting the IL-33 and ferroptosis pathways.
在哮喘病理生理学背景下，尤其是在发作期和气道炎症期间，白细胞介素-33（IL-33）起着关键作用。本研究深入探讨IL-33在哮喘发作期对铁死亡的影响。通过全面的转录组学和蛋白质组学分析，IL-33和谷胱甘肽过氧化物酶4（GPX4）成为这一复杂过程中的关键调节因子。体外实验表明，IL-33抗体在白细胞介素-13诱导的BEAS-2B细胞中具有显著的抗炎和减轻铁死亡的作用。随后在小鼠体内进行的验证强调了IL-33抗体减少炎症反应、增强GPX4表达以及改善哮喘症状的能力。这些令人信服的发现表明，IL-33抗体有望抑制铁死亡、减轻炎症并调节GPX4表达，从而提出通过靶向IL-33和铁死亡途径来管理哮喘发作的新治疗策略。
