J Otolaryngol Ophthalmol Shandong Univ ›› 2018, Vol. 32 ›› Issue (4): 17-23.doi: 10.6040/j.issn.1673-3770.0.2018.183

Previous Articles     Next Articles

Transcription factor NKX2-1 regulates eosinophilic inflammation in chronic rhinosinusitis with nasal polyps

HUANG Yuan1, BA Luo2, LI Bo3, YU Wenxing1, YANG Fangli2, DU Jintao3   

  1. Department of Otorhinolaryngology, Tibet Autonomous Region Peoples Hospital, Lhasa 850000, Tibet, China;3. Department of Otolaryngology Head and Neck Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China
  • Received:2018-04-16 Online:2018-07-20 Published:2018-07-20

PDF (PC)

157

Abstract: Objective To define the endotypes of chronic rhinosinusitis with nasal polyps(CRSwNP)on the basis of the expression of different key cytokines, and to investigate the mechanism via which the new transcription factor, NKX2-1, orchestrates eosinophilic inflammation in nasal polyps(NPs). Methods Polyp tissue was obtained from patients with nasal polyps and turbinate tissue was obtained from the controls after functional nasal endoscopic surgery. The expression levels of key cytokines(IL-5, IFN-γ, and IL-17A,)as well as NKX2-1 and CCL17 in NPs of different endotypes and control tissues were determined using enzyme-linked immunosorbent assay,immunohistochemistry, and western blot analysis. Results We observed that 24% patients with CRSwNP were IL-5 positive and showed infiltration of eosinophilic cells and increased IL-4 and IgE levels; 40% NPs were negative for key cytokines(KCNNPs)but showed increased levels of IL-8 and IL-1β and no eosinophilic inflammation. The expression of NKX2-1 in IL-5 + NPs was significantly lower than in normal controls. Moreover, the expression of CCL17 was significantly higher in IL-5 + NPs, which was associated with reduced NKX2-1 expression and eosinophil accumulation. Conclusion The downregulation of NKX2-1 in IL-5+ NPs may be associated with tissue eosinophilic inflammation. This indicates that NKX2-1 might be a special factor in NP pathophysiology.

Key words: Cytokine, NKX2-1, Nasal polyps, Endotype

CLC Number: 

  • R765.4
[1] Shi JB, Fu QL, Zhang H, et al. Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities[J]. Allergy, 2015, 70(5):533-539.
[2] Bachert C, Zhang N, Holtappels G, et al. Presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in nasal polyps is associated with comorbid asthma[J]. J Allergy Clin Immunol, 2010, 126(5):962-968.
[3] Maeda Y, Chen G, Xu Y, et al. Airway epithelial transcription factor NK2 homeobox 1 inhibits mucous cell metaplasia and Th2 inflammation[J]. Am J Respir Crit Care Med, 2011, 184(4):421-429.
[4] Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists[J]. Rhinology, 2012, 50(1):1-12.
[5] 李华斌, 赖玉婷. 慢性鼻-鼻窦炎的发病机制及诊疗进展[J]. 山东大学耳鼻喉眼学报, 2018, 32(3): 4-9. LI Huabin, LAI Yuting. Pathogenesis, diagnosis, and treatment of chronic rhinosinusitis[J]. J Otolaryngol Ophthalmol Shandong Univ, 2018, 32(3):4-9.
[6] Kim DW, Cho SH. Emerging endotypes of chronic rhinosinusitis and its application to precision medicine[J]. Allergy Asthma Immunol Res, 2017, 9(4):299-306.
[7] Bachert C, Akdis CA. Phenotypes and emerging endotypes of chronic rhinosinusitis[J]. J Allergy Clin Immunol Pract, 2016, 4(4):621-628.
[8] Zhang N, Van Zele T, Perez-Novo C, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease[J]. J Allergy Clin Immunol, 2008, 122(5):961-968.
[9] Zhang N, Holtappels G, Claeys C, et al. Pattern of inflammation and impact of Staphylococcus aureus enterotoxins in nasal polyps from southern China[J]. Am J Rhinol, 2006, 20(4):445-450.
[10] Ba L, Zhang N, Meng J, et al. The association between bacterial colonization and inflammatory pattern in Chinese chronic rhinosinusitis patients with nasal polyps[J]. Allergy, 2011, 66(10):1296-1303.
[11] Cao PP, Li HB, Wang BF, et al. Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese[J]. J Allergy Clin Immunol, 2009, 124(3):478-484.
[12] Shi LL, Xiong P, Zhang L, et al. Features of airway remodeling in different types of Chinese chronic rhinosinusitis are associated with inflammation patterns[J]. Allergy, 2013, 68(1):101-109.
[13] Yoshimura K, Kawata R, Haruna S, et al. Clinical epidemiological study of 553 patients with chronic rhinosinusitis in Japan[J]. Allergy Int, 2011, 60(4):491-496.
[14] Kim JW, Hong SL, Kim YK, et al. Histological and immunological features of non-eosinophilic nasal polyps[J]. Otolaryngol Head Neck Surg, 2007, 137(6):925-930.
[15] Katotomichelakis M, Tantilipikorn P, Holtappels G, et al. Inflammatory patterns in upper airway disease in the same geographical area may change over time[J]. Am J Rhinol Allergy, 2013, 27(5):354-360.
[16] Mahdavinia M, Suh LA, Carter RG, et al. Increased noneosinophilic nasal polyps in chronic rhinosinusitis in US second-generation Asians suggest genetic regulation of eosinophilia[J]. J Allergy Clin Immunol, 2015, 135(2):576-579.
[17] Fernandez LP, López-Márquez A, Santisteban P. Thyroid transcription factors in development, differentiation and disease[J]. Nat Rev Endocrinol, 2015, 11(1):29-42.
[18] Salerno T, Peca D, Menchini L, et al. Respiratory insufficiency in a newborn with congenital hypothyroidism due to a new mutation of TTF-1/NKX2.1 gene[J]. Pediatr Pulmonol, 2014, 49(3):42-44.
[19] Varma S, Cao Y, Tagne JB, et al. The transcription factors Grainyhead-like 2 and NK2-homeobox 1 form a regulatory loop that coordinates lung epithelial cell morphogenesis and differentiation[J]. J Biol Chem, 2012, 287(44):37282-37295.
[20] Wert SE, Dey CR, Blair PA, et al. Increased expression of thyroid transcription factor-1(TTF-1)in respiratory epithelial cells inhibits alveolarization and causes pulmonary inflammation[J]. Dev Biol, 2002, 242(2):75-87.
[21] Sekiya T, Miyamasu M, Imanishi M, et al. Inducible expression of a Th2-type CC chemokine thymus- and activation-regulated chemokine by human bronchial epithelial cells[J]. J Immunol, 2000, 165(4):2205-2213.
[22] Kawasaki S, Takizawa H, Yoneyama H, et al. Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice[J]. J Immunol, 2001, 166(3):2055-2062.
[1] SONG Xiaoyu, ZHANG Yu, LI Chenglin, SONG Xicheng. Enhanced recovery after surgery for the treatment of chronic rhinosinusitis with nasal polyps [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(5): 9-12.
[2] CHEN Wangxing, ZHAO Xue, LIU Yan, LIU Yue, JIN Chunshun. Psychological status of patients with deviated nasal septum or chronic sinusitis with nasal polyps [J]. J Otolaryngol Ophthalmol Shandong Univ, 2018, 32(4): 24-27.
[3] Effect of short-term glucocorticoid inhalation on nasal symptoms and adrenocortical function in patients with eosinophilic chronic sinusitis accompanied by nasal polyps. Effect of short-term glucocorticoid inhalation on nasal symptoms and adrenocortical function in patients with eosinophilic chronic sinusitis accompanied by nasal polyps [J]. J Otolaryngol Ophthalmol Shandong Univ, 2018, 32(4): 28-31.
[4] LOU Hongfei, WANG Chengshuo. Progress in classification of chronic sinusitis [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2018, 32(3): 10-13.
[5] LI Huabin, LAI Yuting. Pathogenesis, diagnosis, and treatment of chronic rhinosinusitis [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2018, 32(3): 4-9.
[6] YU Qianqian, GUAN Ge, ZHANG Niankai, LI Na, WEN Junfeng, LIU Tingting, LIAN Yuanyuan. Characteristics of respiratory epithelial adenomatoid hamartomas in the nasal olfactory cleft on computed tomography [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2018, 32(3): 76-81.
[7] LI Hongmei, WANG Lan, GAO Zhaohui, WANG Ying, XUE Jinmei. The expression and significance of p-ERK2/ ERK2 in nasal polyps [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2018, 32(3): 42-46.
[8] ZHANG Jie, GONG Qi. Clinical significance of eosinophils and neutrophils in blood and allergic reaction in patients with chronic rhinosinusitis [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2018, 32(3): 54-57.
[9] GAN Bin, ZHANG Yongju, XU Anting. BRF2 in the pathogenesis of chronic rhinosinusitis with nasal polyps [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2018, 32(3): 47-53.
[10] ZHI Lili, SONG Daoliang. Expressions of eosinophils and IL5 in antrochoanal polyps and nasal polyps. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2017, 31(4): 43-46.
[11] LUN Jie, ZHANG Ya′nan. Analysis on the factors related to the recurrence of chronic rhinosinusitis with nasal polyps. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2017, 31(3): 80-83.
[12] . The aqueous levels of TNF-α and IP-10 in different kinds of glaucoma and their correlation. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2017, 31(1): 103-106.
[13] LIU Ye, SUN Dianshui, YIN Jinjun, XIA Ming, XU Ying, SUN Jianhua. Vestibular function damage mechanisms in nasopharyngeal carcinoma patients after intensity-modulated radiotherapy. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(6): 14-17.
[14] WANG Haipeng, XU Huijuan, ZHANG Xiufang, WANG Huizhong, LI Yanzhong. The application of Sinus Jel in adult patients of nasal polyps with sleep-disordered breathing. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(5): 58-60.
[15] SU Yi, XIE Jinghua, PAN Xiaoli, ZENG Guoqing. Efficacy and associated factors of endoscopic sinus surgery on patients with chronic rhinosinusitis with or without nasal polyps. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(4): 86-89.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Website Copyright: Editorial Office of Journal of Otolaryngology and Ophthalmology of Shandong University
Address: No.27 Shanda South Road, Jinan, Shandong, China. Post code: 250100 Tel: +86-0531-88366912 Email: ebhxb@sdu.edu.cn Supported by Beijing Magtech Co.Ltd