Abstract 4-Octyl itaconate (4-OI) is a derivative of the Krebs cycle–derived metabolite itaconate and displays an array of antimicrobial and anti-inflammatory properties through modifying cysteine residues within protein targets. We have found that 4-OI significantly reduces the production of eosinophil-targeted chemokines in a variety of cell types, including M1 and M2 macrophages, Th2 cells, and A549 respiratory epithelial cells. Notably, the suppression of these chemokines in M1 macrophages was found to be NRF2-dependent. In addition, 4-OI can interfere with IL-5 signaling and directly affect eosinophil differentiation. In a model of eosinophilic airway inflammation in BALB/c mice, 4-OI alleviated airway resistance and reduced eosinophil recruitment to the lungs. Our findings suggest that itaconate derivatives could be promising therapeutic agents for the treatment of eosinophilic asthma.

中文翻译：

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衣康酸 4-辛酯通过抑制趋化因子和嗜酸性粒细胞发育来减轻气道嗜酸性粒细胞炎症


摘要衣康酸 4-辛酯 (4-OI) 是克雷布斯循环代谢物衣康酸的衍生物，通过修饰蛋白质靶标内的半胱氨酸残基，显示出一系列抗菌和抗炎特性。我们发现 4-OI 显着减少多种细胞类型（包括 M1 和 M2 巨噬细胞、Th2 细胞和 A549 呼吸道上皮细胞）中嗜酸性粒细胞靶向趋化因子的产生。值得注意的是，M1 巨噬细胞中这些趋化因子的抑制被发现是 NRF2 依赖性的。此外，4-OI可以干扰IL-5信号传导并直接影响嗜酸性粒细胞分化。在 BALB/c 小鼠的嗜酸性粒细胞气道炎症模型中，4-OI 减轻了气道阻力并减少了嗜酸性粒细胞向肺部的募集。我们的研究结果表明，衣康酸衍生物可能成为治疗嗜酸性粒细胞性哮喘的有前途的治疗剂。