Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
Int Immunopharmacol. 2013 Nov;17(3):885-93. doi: 10.1016/j.intimp.2013.09.003. Epub 2013 Oct 3.
Heat shock protein 70 (HSP70) plays a critical role in the process of inflammation and innate immunity response under environmental stress.
This study was to investigate HSP70 expression in the peripheral lung tissues of chronic obstructive pulmonary disease (COPD) patients and in human bronchial epithelial cells (16-HBE) exposed to cigarette smoke extract (CSE).
Peripheral lung tissues were collected after lung cancer resection from 26 patients without COPD, 20 with mild COPD and 15 with advanced COPD, classified by lung function criteria. Among these cases, 37 were smokers and 24 non-smokers. Lung tissues were examined for histopathological changes and levels of HSP70 and IL-8. Cultured 16-HBE cells were stimulated with CSE in the absence or presence of HSP70 neutralizing antibody and the expressions of IL-8 and phospho-EGFR protein were determined.
Compared to patients without COPD, the levels of HSP70 and IL-8 were significantly increased in the lung tissues of COPD patients and positively correlated with the severity of the disease. The HSP70 expression was significantly higher in current smokers than that in non-smokers. Moreover, CSE-induced HSP70 significantly enhanced IL-8 production and EGFR phosphorylation in 16-HBE cells. The increases in IL-8 and phospho-EGFR were blocked by anti-HSP70 antibody.
Our study clarified that increased expression of HSP70 is closely related to COPD disease severity and smoking status. Extracellular HSP70 regulated chemokine productions and EGFR phosphorylation and plays an important role in the CSE-induced inflammatory and innate immunity responses in bronchial epithelia cells.
热休克蛋白 70（HSP70）在环境应激下的炎症和固有免疫反应过程中发挥着关键作用。
本研究旨在探讨慢性阻塞性肺疾病（COPD）患者外周肺组织以及暴露于香烟烟雾提取物（CSE）的人支气管上皮细胞（16-HBE）中 HSP70 的表达。
从 26 例肺癌切除术后无 COPD 的患者、20 例轻度 COPD 患者和 15 例晚期 COPD 患者中收集外周肺组织，根据肺功能标准进行分类。其中吸烟者 37 例，非吸烟者 24 例。检查肺组织的组织病理学变化以及 HSP70 和 IL-8 的水平。用 CSE 刺激培养的 16-HBE 细胞，在存在或不存在 HSP70 中和抗体的情况下，测定 IL-8 和磷酸化 EGFR 蛋白的表达。
与无 COPD 的患者相比，COPD 患者肺组织中 HSP70 和 IL-8 的水平显著升高，且与疾病的严重程度呈正相关。HSP70 的表达在现吸烟者中明显高于非吸烟者。此外，CSE 诱导的 HSP70 显著增强了 16-HBE 细胞中 IL-8 的产生和 EGFR 的磷酸化。抗 HSP70 抗体阻断了 IL-8 和磷酸化 EGFR 的增加。
本研究表明，HSP70 的表达增加与 COPD 疾病的严重程度和吸烟状况密切相关。细胞外 HSP70 调节趋化因子的产生和 EGFR 磷酸化，在支气管上皮细胞中 CSE 诱导的炎症和固有免疫反应中发挥重要作用。
