团队多种族研究证实IL-8作为共有免疫学分子靶标在慢性鼻窦炎伴鼻息肉（CRSwNP）中起重要作用。前期亚硫酸修饰-焦磷酸测序发现鼻上皮细胞IL8启动子去甲基化与CRSwNP相关；IL-1beta可诱导IL8启动子去甲基化，去甲基化提高转录因子OCT1和p65结合效力，上调IL8基因表达。由此提出假说：IL-1beta信号通路可以通过调控IL8启动子去甲基化参与CRSwNP发病。本研究拟明确鼻粘膜上皮IL8启动子去甲基化与CRSwNP的内在联系；构建鼻上皮细胞气液培养体系，通过IL-1beta信号通路拮抗、siRNA等干预实验，确定IL-1beta调控IL8去甲基化的具体信号通路；利用双荧光素酶报告基因、EMSA等实验阐明IL8去甲基化影响基因表达的分子机制；采用NP组织块培养，确定拮抗IL-8对CRSwNP的治疗作用。本研究从表观遗传学方面为CRSwNP的发病机制理解、个体化防治提供新靶。

Our previous multi-ethnic study suggests that elevated IL-8 protein concentrations in patients with chronic rhinosinusitis with nasal polyps （CRSwNP）are the only common feature of TH cytokine profiles in different ethnicities. The preliminary experiments using bisulfite pyrosequencing showed that the hypomethylation of IL8 promoter in human nasal epithelial cells (HNECs) was significantly associated with CRSwNP and inflammation cells infiltration. IL-1beta significantly increased IL8 gene expression accompanied by reduction in methylation of IL8 promoter that changed the binding OCT1 and p65. Therefore, we hypothesize that IL-1 beta mediated pathways are able to regulate the methylation status of IL8 promoter in CRSwNP. In the present study, we will investigate the concrete relationship between the hypomethylation of IL8 promoter in HNECs and CRSwNP. We will plan to focus on how the IL-1 beta regulates DNA methyltransferase (DNMTs) and which signaling pathway plays the role in HNECs air-liquid interface cultures by using IL-1 beta pathway antagonists and siRNA technique. We will determine the regulatory effect of hypomethylation of IL8 promoter on IL8 gene expression through double luciferase reporter gene, EMSA and et al.experiments. Finally, we will investigate the treatment of IL-8 intervention on CRSwNP. The research will provide new epigenetic molecular targets regarding the prevention and treatment of CRSwNP.