CRYAB 通过抑制 PI3K/Akt 和 NF-κB 信号通路来减少香烟烟雾诱导的人支气管上皮细胞的炎症、细胞凋亡和氧化应激。
CRYAB reduces cigarette smoke-induced inflammation, apoptosis, and oxidative stress by retarding PI3K/Akt and NF-κB signaling pathways in human bronchial epithelial cells.
机构信息
Department of Cardiothoracic Surgery, Tongji Hospital Affiliated to Tongji University, Shanghai, China.
Department of Respiratory and Critical Care Medicine, Lishui City People's Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui, Zhejiang Province, China;
出版信息
Allergol Immunopathol (Madr). 2022 Sep 1;50(5):23-29. doi: 10.15586/aei.v50i5.645. eCollection 2022.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a familiar airway disease characterized by chronic immune response in the lungs. More and more evidences have assured that cigarette smoking is the primary reason for the progression of COPD, but its related regulatory mechanism requires further clarification. The α-B-crystallin (CRYAB) has been identified to exhibit vital functions in different diseases, and is down-regulated in the alveoli of mice mediated by cigarette smoke extract (CSE).
METHODS
The messenger RNA expression of CRYAB was assessed by reverse transcription--quantitative polymerase chain reaction. The proteins' expressions were tested using Western blot method. The cytotoxicity was measured by lactate dehydrogenase assay. The levels of malondialdehyde, superoxide dismutase, catalase, myeloperoxidase, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were assessed through enzyme-linked-immunosorbent serologic assay (ELISA).
RESULTS
In this study, it was discovered that the expression of CRYAB was markedly decreased with the increased time of cigarette smoking. Moreover, CRYAB overexpression increased cell viability and decreased cell apoptosis induced by cigarette smoke. In addition, the strengthened oxidative stress and inflammation mediated by CSE treatment was relieved after overexpression of CRYAB. Eventually, results OF Western blot method confirmed that CRYAB retarded the activation of phosphatidylinositol 3-kinase-Ak strain transforming (PI3K-Akt) and nuclear factor kappa B (NF-κB) signaling pathways.
CONCLUSION
Our results manifested that CRYAB reduced cigarette smoke-induced inflammation, apoptosis, and oxidative stress in normal and diseased bronchial epithelial (NHBE) and human bronchial epithelial (BEAS-2B) cells by suppressing PI3K/Akt and NF-κB signaling pathways, which highlighted the functioning of CRYAB in preventing or treating COPD.
背景
慢性阻塞性肺疾病（COPD）是一种常见的气道疾病，其特征为肺部慢性免疫反应。越来越多的证据表明，吸烟是 COPD 进展的主要原因，但相关的调节机制仍需进一步阐明。α-B-晶体蛋白（CRYAB）在不同疾病中表现出重要功能，并且在香烟烟雾提取物（CSE）介导的小鼠肺泡中下调。
方法
采用反转录-定量聚合酶链反应检测 CRYAB 的信使 RNA 表达。采用 Western blot 法检测蛋白质表达。通过乳酸脱氢酶测定法检测细胞毒性。通过酶联免疫吸附试验（ELISA）检测丙二醛、超氧化物歧化酶、过氧化氢酶、髓过氧化物酶、肿瘤坏死因子-α、白细胞介素（IL）-1β和 IL-6 的水平。
结果
在这项研究中，发现 CRYAB 的表达随着吸烟时间的增加而明显降低。此外，CRYAB 过表达增加了香烟烟雾诱导的细胞活力并降低了细胞凋亡。此外，CSE 处理后增强的氧化应激和炎症在 CRYAB 过表达后得到缓解。最终，Western blot 法的结果证实，CRYAB 抑制了磷脂酰肌醇 3-激酶-Akt 转化（PI3K-Akt）和核因子 kappa B（NF-κB）信号通路的激活。
结论
我们的结果表明，CRYAB 通过抑制 PI3K/Akt 和 NF-κB 信号通路，减少正常和患病支气管上皮（NHBE）和人支气管上皮（BEAS-2B）细胞中香烟烟雾诱导的炎症、凋亡和氧化应激，强调了 CRYAB 在预防或治疗 COPD 中的作用。
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