Patergnani Simone, Vitto Veronica A M, Pinton Paolo, Rimessi Alessandro
Department of Medical Sciences and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
Center of Research for Innovative Therapies in Cystic Fibrosis, University of Ferrara, Ferrara, Italy.
Front Pharmacol. 2020 Sep 30;11:581114. doi: 10.3389/fphar.2020.581114. eCollection 2020.
Cystic fibrosis (CF) is a genetic disease associated to mutations in the cystic fibrosis transmembrane conductance regulator gene, which results in the alteration of biological fluid and electrolyte homeostasis. The characteristic pathological manifestation is represented by exaggerated proinflammatory response in lung of CF patients, driven by recurrent infections and worsen by hypersecretion of proinflammatory mediators and progressive tissue destruction. Treating inflammation remains a priority in CF. However, current anti-inflammatory treatments, including non-steroidal agents, are poorly effective and present dramatic side effects in CF patients. Different studies suggest an intimate relationship between mitochondria and CF lung disease, supporting the hypothesis that a decline in mitochondrial function endorses the development of the hyperinflammatory phenotype observed in CF lung. This allowed the implementation of a new concept: the "mito-inflammation," a compartmentalization of inflammatory process, related to the role of mitochondria in engage and sustain the inflammatory responses, resulting a druggable target to counteract the amplification of inflammatory signals in CF. Here, we will offer an overview of the contribution of mitochondria in the pathogenesis of CF lung disease, delving into mitochondrial quality control responses, which concur significantly to exacerbation of CF lung inflammatory responses. Finally, we will discuss the new therapeutic avenues that aim to target the mito-inflammation, an alternative therapeutic advantage for mitochondrial quality control that improves CF patient's inflammatory state.
囊性纤维化（CF）是一种与囊性纤维化跨膜传导调节因子基因突变相关的遗传性疾病，该突变导致生物体液和电解质稳态的改变。其特征性病理表现为CF患者肺部过度的促炎反应，由反复感染驱动，并因促炎介质的分泌过多和进行性组织破坏而恶化。治疗炎症仍然是CF治疗的首要任务。然而，目前的抗炎治疗，包括非甾体类药物，效果不佳，且在CF患者中存在严重的副作用。不同的研究表明线粒体与CF肺部疾病之间存在密切关系，支持了线粒体功能下降促进CF肺部观察到的高炎症表型发展这一假说。这催生了一个新的概念：“线粒体炎症”，即炎症过程的区室化，与线粒体在参与和维持炎症反应中的作用有关，从而成为对抗CF中炎症信号放大的一个可药物作用靶点。在此，我们将概述线粒体在CF肺部疾病发病机制中的作用，深入探讨线粒体质量控制反应，其在很大程度上加剧了CF肺部的炎症反应。最后，我们将讨论旨在靶向线粒体炎症的新治疗途径，这是一种改善CF患者炎症状态的线粒体质量控制的替代治疗优势。
