山东大学耳鼻喉眼学报 ›› 2018, Vol. 32 ›› Issue (4): 17-23.doi: 10.6040/j.issn.1673-3770.0.2018.183

• ·论著· • 上一篇    下一篇

慢性鼻窦炎鼻息肉中转录因子NKX2-1调控嗜酸性炎症反应的作用

黄远1,巴罗2,李波3,余文兴1,杨芳丽2,杜进涛3   

  1. 81560172);
    中国博士后科学基金项目(2014M552363)第一作者:黄远。 E-mail:basangnorpu88@sina.com通讯作者:巴罗。 E-mail:bhanor@163.comDOI:10.6040/j.issn.1673-3770.0.2018.183慢性鼻窦炎鼻息肉中转录因子NKX2-1调控嗜酸性炎症反应的作用黄远1, 巴罗2, 李波3, 余文兴1, 杨芳丽2, 杜进涛3(1.遂宁市中心医院耳鼻咽喉头颈外科, 四川 遂宁 629000;
    2.西藏自治区人民医院耳鼻咽喉科, 西藏 拉萨 850000;
    3.四川大学华西医院耳鼻咽喉头颈外科, 四川 成都 610041
  • 收稿日期:2018-04-16 出版日期:2018-07-20 发布日期:2018-07-20
  • 通讯作者: 巴罗. E-mail:bhanor@163.com
  • 基金资助:
    国家自然科学基金项目(81560172);中国博士后科学基金项目(2014M552363)

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

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摘要： 目的 研究新型转录因子NKX2-1在慢性鼻窦炎伴鼻息肉发病中调控嗜酸性免疫炎症反应的作用。 方法 功能性鼻内镜手术获取鼻息肉及非变应性单纯鼻中隔偏曲患者鼻甲标本,通过酶联免疫、免疫组化及蛋白印迹检测细胞因子IL-5、IFN-γ、IL-17A,转录因子NKX2-1及趋化因子CCL17在患者中的表达。 结果 鼻息肉患者中IL-5阳性表达率为24%,并伴有IL-4、IgE等炎症介质及酸性粒细胞浸润升高特征;40%鼻息肉患者关键细胞因子阴性表达并伴有IL-1β、IL-8等非嗜酸性炎症升高特征。单纯IL-5+鼻息肉患者NKX2-1表达低于非变应性单纯鼻中隔偏曲患者,单纯IL-5+鼻息肉患者中趋化因子CCL17高于非变应性单纯鼻中隔偏曲患者,且与趋化嗜酸性粒细胞相关。 结论 新型转录因子NKX2-1在不同内在型鼻息肉患者中具有表达差异,其在单纯IL-5+鼻息肉患者中表达下降且有负性调控嗜酸性炎症反应作用。

关键词: 鼻息肉, 内在型, 细胞因子, NKX2-1

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

中图分类号: 

  • 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.
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