Hypomethylation of the IL8 promoter in nasal epithelial cells of patients with chronic rhinosinusitis with nasal polyps

被引：25
作者：
Li, Jingyun [1 ,3 ]
Jiao, Jian [1 ,3 ]
Wang, Ming [1 ,3 ]
Gao, Yunbo [1 ,3 ]
Li, Ying [1 ,3 ]
Wang, Yang [1 ,3 ]
Zhang, Yuan [1 ,2 ,3 ]
Wang, Xiangdong [1 ,2 ,3 ]
Zhang, Luo [1 ,2 ,3 ]
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
来源：
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2019年 / 144卷 / 04期
基金：
北京市自然科学基金; 国家重点研发计划; 中国国家自然科学基金;
关键词：
Chronic rhinosinusitis; DNA methylation; Han Chinese; human nasal epithelial cells; IL-8 proximal promoter; nuclear factor kappa B; Octamer-binding transcription factor 1; NF-KAPPA-B; DNA METHYLATION STATUS; PROTEIN EXPRESSION; GENE-EXPRESSION; INTERLEUKIN-8; TRANSCRIPTION; OCT-1; ACTIVATION; BINDING; INFLAMMATION;
D O I：
10.1016/j.jaci.2019.06.042
中图分类号：
R392 [医学免疫学];
学科分类号：
100102 ;
摘要：
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.
引用
收藏
页码：993 / +
页数：23
相关论文
共 42 条
[1]   DNA Methylation Status of the IL8 Gene Promoter in Aggressive Periodontitis [J].
Andia, Denise C. ;
de Oliveira, Naila F. P. ;
Casarin, Renato C. V. ;
Casati, Marcio Z. ;
Line, Sergio R. P. ;
de Souza, Ana P. .
JOURNAL OF PERIODONTOLOGY, 2010, 81 (09) :1336-1341
[2]   ICON: chronic rhinosinusitis [J].
Bachert, Claus ;
Pawankar, Ruby ;
Zhang, Luo ;
Bunnag, Chaweewan ;
Fokkens, Wytske J. ;
Hamilos, Daniel L. ;
Jirapongsananuruk, Orathai ;
Kern, Robert ;
Meltzer, Eli O. ;
Mullol, Joaquim ;
Naclerio, Robert ;
Pilan, Renata ;
Rhee, Chae-Seo ;
Suzaki, Harumi ;
Voegels, Richard ;
Blaiss, Michael .
WORLD ALLERGY ORGANIZATION JOURNAL, 2014, 7
[3]   Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese [J].
Cao, Ping-Ping ;
Li, Hua-Bin ;
Wang, Bao-Feng ;
Wang, Shui-Bin ;
You, Xue-Jun ;
Cui, Yong-Hua ;
Wang, De-Yun ;
Desrosiers, Martin ;
Liu, Zheng .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 124 (03) :478-U135
[4]   Methylation of cytokines gene promoters in IL-1β-treated human intestinal epithelial cells [J].
Caradonna, Fabio ;
Cruciata, Ilenia ;
Schifano, Ilaria ;
La Rosa, Chiara ;
Naselli, Flores ;
Chiarelli, Roberto ;
Perrone, Anna ;
Gentile, Carla .
INFLAMMATION RESEARCH, 2018, 67 (04) :327-337
[5]   Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics [J].
Cheong, H. S. ;
Park, S. -M. ;
Kim, M. -O. ;
Park, J. -S. ;
Lee, J. Y. ;
Byun, J. Y. ;
Park, B. L. ;
Shin, H. D. ;
Park, C. -S. .
ALLERGY, 2011, 66 (05) :637-644
[6]   CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: regulation by BET [J].
Clifford, Rachel L. ;
Patel, Jamie K. ;
John, Alison E. ;
Tatler, Amanda L. ;
Mazengarb, Lisa ;
Brightling, Christopher E. ;
Knox, Alan J. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2015, 308 (09) :L962-L972
[7]   DNA promoter methylation status and protein expression of interleukin-8 in human colorectal adenocarcinomas [J].
Dimberg, Jan ;
Strom, Karin ;
Lofgren, Sture ;
Zar, Niklas ;
Lindh, Mikael ;
Matussek, Andreas .
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 2012, 27 (06) :709-714
[8]   Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA2LEN survey [J].
Ek, A. ;
Middelveld, R. J. M. ;
Bertilsson, H. ;
Bjerg, A. ;
Ekerljung, L. ;
Malinovschi, A. ;
Stjarne, P. ;
Larsson, K. ;
Dahlen, S. -E. ;
Janson, C. .
ALLERGY, 2013, 68 (10) :1314-1321
[9]   INTERLEUKIN-8 IS A POTENT MEDIATOR OF EOSINOPHIL CHEMOTAXIS THROUGH ENDOTHELIUM AND EPITHELIUM [J].
ERGER, RA ;
CASALE, TB .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1995, 268 (01) :L117-L122
[10]   European Position Paper on Rhinosinusitis and Nasal Polyps 2020 [J].
Fokkens, Wytske J. ;
Lund, Valerie J. ;
Hopkins, Claire ;
Hellings, Peter W. ;
Kern, Robert ;
Reitsma, Sietze ;
Toppila-Salmi, Sanna ;
Bernal-Sprekelsen, Manuel ;
Mullol, Joaquim ;
Alobid, Isam ;
Anselmo-Lima, Wilma Terezinha ;
Bachert, Claus ;
Baroody, Fuad ;
von Buchwald, Christian ;
Cervin, Anders ;
Cohen, Noam ;
Constantinidis, Jannis ;
De Gabory, Ludovic ;
Desrosiers, Martin ;
Diamant, Zuzana ;
Douglas, Richard G. ;
Gevaert, Philippe H. ;
Hafner, Anita ;
Harvey, Richard J. ;
Joos, Guy F. ;
Kalogjera, Livije ;
Knill, Andrew ;
Kocks, Janwillem H. ;
Landis, Basile N. ;
Limpens, Jacqueline ;
Lebeer, Sarah ;
Lourenco, Olga ;
Matricardi, Paolo M. ;
Meco, Cem ;
O'Mahony, Liam ;
Philpott, Carl M. ;
Ryan, Dermot ;
Schlosser, Rodney ;
Senior, Brent ;
Smith, Timothy L. ;
Teeling, Thijs ;
Tomazic, Peter Valentin ;
Wang, De Yun ;
Wang, Dehui ;
Zhang, Luo ;
Agius, Adrian M. ;
Ahlstrom-Emanuelsson, Cecilia ;
Alabri, Rashid ;
Albu, Silviu ;
Alhabash, Saied .
RHINOLOGY, 2020, 58 :1-464
12345