Background: IL-8 is an important chemokine implicated in the pathogenesis of chronic rhinosinusitis (CRS), but little is known about epigenetic regulation of IL8 in the pathogenesis of CRS. Objective: We sought to investigate the relationship between the DNA methylation level in the IL8 proximal promoter and CRS in Han Chinese subjects. Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP; n = 187), patients with chronic rhinosinusitis without nasal polyps (CRSsNP; n = 89), and control subjects (n = 57) were enrolled in 2 independent cohorts. Purified human nasal epithelial cells from each participant were assessed for percentage DNA methylation of CpG sites in the IL8 proximal promoter by using bisulfite pyrosequencing and for functional aspects of methylation status by using in vitro assays. Results: DNA methylation of CpG sites 1, 2, and 3, respectively, in the IL8 proximal promoter was significantly decreased in human nasal epithelial cells of patients with CRSwNP compared with that in patients with CRSsNP (P < .001) and control subjects (P < .001). Percentage of DNA methylation of the CpG3 site was correlated negatively with both tissue eosinophilic cationic protein (P < .01) and myeloperoxidase (P < .05) levels. IL-1 beta (P < .001) and TNF-alpha (P < .01) significantly increased IL8 expression accompanied by a reduction in methylation at the CpG3 site (P < .001). Electrophoretic mobility shift assays demonstrated that methylation status of CpG3 changed the binding of octamer-binding transcription factor 1 and nuclear factor kappa B. Conclusion: Decreased DNA methylation of particularly CpG sites in the IL8 proximal promoter might play a role in the pathogenesis of CRSwNP.
基金：
Beijing Natural Science FoundationBeijing Natural Science Foundation [7182034, 7172054, 7172053]; National Key R&D Program of China [2016YFC20160905200]; Program for the Changjiang Scholars and Innovative Research TeamProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT13082]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81420108009, 81630023, 81400447, 81570894, 81570895]; Beijing Municipal Administration of Hospitals' Mission Plan [SML20150203]; Beijing Advanced Innovation Center for Food Nutrition and Human Health (Beijing Technology and Business University) [20181045]; Beijing Health Bureau Program for High Level Talents [2014-3-018]; Cross-disciplinary Collaborative Program of Beijing Nova program [xxjc201712]
第一作者机构：[1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China[3]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China[2]Capital Med Univ, Beijing TongRen Hosp, Dept Allergy, Beijing, Peoples R China[3]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing, Peoples R China[*1]Beijing Inst Otolaryngol, 17 HouGouHuTong, Beijing 100005, Peoples R China
推荐引用方式(GB/T 7714)：
Li Jingyun,Jiao Jian,Wang Ming,et al.Hypomethylation of the IL8 promoter in nasal epithelial cells of patients with chronic rhinosinusitis with nasal polyps[J].JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY.2019,144(4):993-+.doi:10.1016/j.jaci.2019.06.042.
APA：
Li, Jingyun,Jiao, Jian,Wang, Ming,Gao, Yunbo,Li, Ying...&Zhang, Luo.(2019).Hypomethylation of the IL8 promoter in nasal epithelial cells of patients with chronic rhinosinusitis with nasal polyps.JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,144,(4)
MLA：
Li, Jingyun,et al."Hypomethylation of the IL8 promoter in nasal epithelial cells of patients with chronic rhinosinusitis with nasal polyps".JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 144..4(2019):993-+
医学