Zhu Lingxiang, Di Peter Y P, Wu Reen, Pinkerton Kent E, Chen Yin
Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, 85721, United States of America.
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, 15219, United States of America.
PLoS One. 2015 Jan 30;10(1):e0116159. doi: 10.1371/journal.pone.0116159. eCollection 2015.
Club (Clara) Cell Secretory Protein (CCSP, or CC16) is produced mainly by non-ciliated airway epithelial cells including bronchiolar club cells and the change of its expression has been shown to associate with the progress and severity of Chronic Obstructive Pulmonary Disease (COPD). In an animal model, the lack of CC16 renders the animal susceptible to the tumorigenic effect of a major CS carcinogen. A recent population-based Tucson Epidemiological Study of Airway Obstructive Diseases (TESAOD) has indicated that the low serum CC16 concentration is closely linked with the smoke-related mortality, particularly that driven by the lung cancer. However, the study of CC16 expression in well-defined smoke exposure models has been lacking, and there is no experimental support for the potential causal link between CC16 and CS-induced pathophysiological changes in the lung. In the present study, we have found that airway CC16 expression was significantly repressed in COPD patients, in monkey CS exposure model, and in CS-induced mouse model of COPD. Additionally, the lack of CC16 exacerbated airway inflammation and alveolar loss in the mouse model. Therefore, CC16 may play an important protective role in CS-related diseases.
克拉拉细胞分泌蛋白（CCSP，或CC16）主要由包括细支气管克拉拉细胞在内的非纤毛气道上皮细胞产生，其表达变化已被证明与慢性阻塞性肺疾病（COPD）的进展和严重程度相关。在动物模型中，缺乏CC16会使动物易受主要香烟致癌物的致瘤作用影响。最近一项基于人群的图森气道阻塞性疾病流行病学研究（TESAOD）表明，血清CC16浓度低与吸烟相关死亡率密切相关，尤其是由肺癌导致的死亡率。然而，缺乏在明确的烟雾暴露模型中对CC16表达的研究，且没有实验支持CC16与香烟烟雾诱导的肺部病理生理变化之间的潜在因果关系。在本研究中，我们发现COPD患者、猴子香烟烟雾暴露模型以及香烟烟雾诱导的COPD小鼠模型中气道CC16表达均显著受到抑制。此外，在小鼠模型中缺乏CC16会加剧气道炎症和肺泡损失。因此，CC16可能在香烟烟雾相关疾病中发挥重要的保护作用。
