哮喘是常见的慢性气道炎症疾病之一，其病理过程伴随DNA损伤反应，但是关于哮喘气道上皮细胞DNA损伤的具体机制仍不明确。细胞因子IL-17在激素治疗不佳的中性粒细胞型哮喘中发挥了重要调控作用。我们前期研究发现，IL-17高表达的中性粒细胞型哮喘小鼠气道上皮存在DNA损伤，但在IL-17基因敲除条件下DNA损伤缓解；此外，IL-17体外可直接诱导DNA损伤，此现象在Lipocalin-2基因沉默之后被抑制。据此我们提出假说：IL-17通过Lipocalin-2介导中性粒细胞型哮喘气道上皮细胞DNA损伤过程。本研究拟从分子、细胞、组织以及动物水平等多层次探索IL-17与Lipocalin-2对哮喘气道炎症的调节，对DNA损伤与修复蛋白表达的调控，对细胞周期、细胞凋亡、染色体形态、DNA复制及其速度的影响。本课题从细胞因子介导DNA损伤的新观点阐述哮喘发病机制，为哮喘的研究与预防治疗提供了新思路。

Asthma is one of the most popular chronic airway inflammation with the complicated pathogenesis such as DNA damage response, however, the mechanisms of DNA damage in epithelium of asthma are poorly understood. Interleukin-17 has been suggested to play an important role in the corticoid-insensitive neutrophilic asthma. Our previous studies have found the DNA damage response in epithelial cells of neutrophilic asthma with the higher-expressed interleukin-17, and which was blocked in IL-17-deficient mice. In addition, we also demonstrated that IL-17 directly induced DNA damage response on epithelial cells in vitro, and this process was inhibited by silencing of Lipocalin-2 gene. Based on these findings, we hypothesized that IL-17-Lipocalin-2 pathway could play an important regulatory role in DNA damage response in asthma. With the various strategies, we intend to evaluate the effects of IL-17 and Lipocalin-2 on airway inflammatory, the expression of DNA damage and repair proteins, the cell cycle, cell apoptosis, chromosome morphology, as well as the DNA replication/ replication speed in asthma. This project will help us to better understand the pathogenesis and treatment of asthma by exploring the regulatory role of cytokine on DNA damage response.