铁和炎症性细胞因子协同诱导结肠炎中的结肠上皮细胞亡
Mo Wang1, Chang Zheng1, Fan Zhou1
1Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
结肠细胞中的铁过载会通过铁亡导致细胞死亡,从而使炎症性肠病 (IBD) 恶化. 这一发现可能解释了为什么口服铁在IBD患者的耐受性很差.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 炎症性肠病 (IBD) 通常导致贫血,需要补充铁.
- 对许多IBD患者来说,口服铁疗法的遵守是个挑战,其潜在机制尚不清楚.
研究的目的:
- 研究结肠上皮层铁过载对细胞活力和IBD严重性的影响.
- 阐明铁过载加剧肠道炎症的机制.
主要方法:
- 使用硫酸德克斯 (DSS) 诱导的急性结肠炎和IL10淘汰赛小鼠模型.
- 采用培养的Caco-2细胞来研究铁和细胞因子相互作用.
- 评估铁进口商,铁积累,细胞死亡,脂质过氧化和谷氨酸水平.
主要成果:
- 在活跃性结肠炎期间,结肠细胞中观察到铁进口者的增加和铁积累.
- 肝素的使用加剧了结肠炎和结肠上皮细胞死亡,抗氧化剂可以预防.
- 铁和炎症性细胞因子通过NOX1依赖的谷氨枯竭协同诱导死细胞死亡,称为ferroptosis.
结论:
- 炎症性肠病创造了一个细胞环境,使结肠细胞倾向于铁过载诱导的铁亡.
- 这种铁亡机制有助于IBD中结肠炎症的恶化.
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