Ramil-Gómez Olalla, López-Pardo Mirian, Fernández-Rodríguez Jennifer Adriana, Rodríguez-Carmona Ana, Pérez-López Teresa, Vaamonde-García Carlos, Pérez-Fontán Miguel, López-Armada María José
Aging and Inflammation Research Laboratory, Institute for Biomedical Research of A Coruña (INIBIC), 15006 A Coruña, Spain.
Endocrine, Nutritional and Metabolic Diseases Group, Faculty of Health Sciences, A Coruña, INIBIC, 15006 A Coruña, Spain.
Antioxidants (Basel). 2022 Nov 4;11(11):2184. doi: 10.3390/antiox11112184.
Recent studies have related mitochondrial impairment with peritoneal membrane damage during peritoneal dialysis (PD) therapy. Here, we assessed the involvement of mitochondrial dysfunction in the inflammatory response in human mesothelial cells, a hallmark in the pathogenesis of PD-related peritoneal membrane damage. Our ex vivo studies showed that IL-1β causes a drop in the mitochondrial membrane potential in cells from peritoneal effluent. Moreover, when mitochondrial damage was induced by inhibitors of mitochondrial function, a low-grade inflammatory response was generated. Interestingly, mitochondrial damage sensitized mesothelial cells, causing a significant increase in the inflammatory response induced by cytokines, in which ROS generation and NF-κB activation appear to be involved, since inflammation was counteracted by both mitoTEMPO (mitochondrial ROS scavenger) and BAY-117085 (NF-κB inhibitor). Furthermore, the natural anti-inflammatory antioxidant resveratrol significantly attenuated the inflammatory response, by reversing the decline in mitochondrial membrane potential and decreasing the expression of IL-8, COX-2 and PGE caused by IL-1β. These findings suggest that IL-1β regulates mitochondrial function in mesothelial cells and that mitochondrial dysfunction could induce an inflammatory scenario that sensitizes these cells, causing significant amplification of the inflammatory response induced by cytokines. Resveratrol may represent a promising strategy in controlling the mesothelial inflammatory response to PD.
近期研究已将线粒体损伤与腹膜透析（PD）治疗期间的腹膜损伤联系起来。在此，我们评估了线粒体功能障碍在人腹膜间皮细胞炎症反应中的作用，这是PD相关腹膜损伤发病机制中的一个标志。我们的体外研究表明，白细胞介素-1β（IL-1β）会导致腹膜透析液中的细胞线粒体膜电位下降。此外，当用线粒体功能抑制剂诱导线粒体损伤时，会产生低度炎症反应。有趣的是，线粒体损伤使间皮细胞敏感化，导致细胞因子诱导的炎症反应显著增加，其中似乎涉及活性氧（ROS）生成和核因子κB（NF-κB）激活，因为线粒体靶向抗氧化剂（mitoTEMPO，线粒体ROS清除剂）和BAY-117085（NF-κB抑制剂）均能对抗炎症。此外，天然抗炎抗氧化剂白藜芦醇通过逆转线粒体膜电位下降并降低IL-1β引起的IL-8、环氧化酶-2（COX-2）和前列腺素E（PGE）的表达，显著减轻了炎症反应。这些发现表明，IL-1β调节间皮细胞中的线粒体功能，线粒体功能障碍可能引发一种炎症状态，使这些细胞敏感化，导致细胞因子诱导的炎症反应显著放大。白藜芦醇可能是控制腹膜间皮细胞对PD炎症反应的一种有前景的策略。
