Guan Xiaoqing, Hou Yuning, Sun Fei, Yang Zhe, Li Chunying
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine. 540 E. Canfield Avenue, 5312 Scott Hall, Detroit, MI 48201, USA.
Curr Drug Targets. 2016;17(13):1535-44. doi: 10.2174/1389450117666151209120516.
CF lung disease is characterized by a chronic and non-resolving activation of the innate immune system with excessive release of chemokines/cytokines including IL-8 and persistent infiltration of immune cells, mainly neutrophils, into the airways. Chronic infection and impaired immune response eventually lead to pulmonary damage characterized by bronchiectasis, emphysema, and lung fibrosis. As a complete knowledge of the pathways responsible for the exaggerated inflammatory response in CF lung disease is lacking, understanding these pathways could reveal new therapeutic targets, and lead to novel treatments. Therefore, there is a strong rationale for the identification of mechanisms and pathways underlying the exaggerated inflammatory response in CF lung disease. This article reviews the role of inflammation in the pathogenesis of CF lung disease, with a focus on the dysregulated signaling involved in the overexpression of chemokine IL-8 and excessive recruitment of neutrophils in CF airways. The findings suggest that targeting the exaggerated IL-8/IL-8 receptor (mainly CXCR2) signaling pathway in immune cells (especially neutrophils) may represent a potential therapeutic strategy for CF lung disease.
囊性纤维化肺部疾病的特征是先天性免疫系统的慢性且无法消退的激活，伴有趋化因子/细胞因子（包括白细胞介素-8）的过度释放，以及免疫细胞（主要是中性粒细胞）持续浸润到气道中。慢性感染和免疫反应受损最终导致以支气管扩张、肺气肿和肺纤维化为特征的肺部损伤。由于缺乏对导致囊性纤维化肺部疾病中过度炎症反应的途径的全面了解，了解这些途径可能会揭示新的治疗靶点，并带来新的治疗方法。因此，有充分的理由去识别囊性纤维化肺部疾病中过度炎症反应背后的机制和途径。本文综述了炎症在囊性纤维化肺部疾病发病机制中的作用，重点关注参与趋化因子白细胞介素-8过表达和囊性纤维化气道中中性粒细胞过度募集的失调信号传导。研究结果表明，针对免疫细胞（尤其是中性粒细胞）中过度的白细胞介素-8/白细胞介素-8受体（主要是CXCR2）信号通路可能是囊性纤维化肺部疾病的一种潜在治疗策略。
