Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2022, Vol. 36 ›› Issue (3): 64-70.doi: 10.6040/j.issn.1673-3770.0.2021.577

Previous Articles     Next Articles

The roles of ion channels in the pathogenesis of chronic rhinosinusitis

LIN Hai, ZHU YingOverview,ZHANG Weitian   

  1. Department of Otorhinolaryngology & Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital/Otolaryngological Institute, Shanghai Jiao Tong University/Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai 200233, China
  • Published:2022-06-15

Abstract: Chronic rhinosinusitis(CRS)is a common chronic inflammatory disease in rhinology; its etiology and pathogenesis are not fully understood. Ion channels are proposed to participate in a variety of physiological activities, such as stabilizing membrane potential, maintaining cellular volume homeostasis, regulating intercellular signal transduction, and other functions. Calcium channels, potassium channels, sodium channels, chloride channels and hydrogen ion-related ion channels are closely related to the pathogenesis of CRS. Numerous studies have shown that ion channels are abnormally expressed in nasal mucosa tissues from CRS patients, indicating that disturbance of ion channel regulation may be involved in the inflammatory immune response of CRS and lead to its further aggravation. This review summarizes research progress on the roles of ion channels in the pathogenesis of CRS. The aim is to provide new insights into further explorations of CRS pathogenesis and treatment strategies.

Key words: Chronic rhinosinusitis, Nasal polyp, Ion, Ion channels, Pathogenesis

CLC Number: 

  • R765.41
[1] Zhang Y, Gevaert E, Lou HF, et al. Chronic rhinosinusitis in Asia[J]. J Allergy Clin Immunol, 2017, 140(5): 1230-1239. doi:10.1016/j.jaci.2017.09.009.
[2] Kato A, Peters AT, Stevens WW, et al. Endotypes of chronic rhinosinusitis: relationships to disease phenotypes, pathogenesis, clinical findings, and treatment approaches[J]. Allergy, 2022, 77(3): 812-826. doi:10.1111/all.15074.
[3] Cho SH, Hamilos DL, Han DH, et al. Phenotypes of chronic rhinosinusitis[J]. J Allergy Clin Immunol Pract, 2020, 8(5): 1505-1511. doi:10.1016/j.jaip.2019.12.021.
[4] Harraz OF, Jensen LJ. Aging, calcium channel signaling and vascular tone[J]. Mech Ageing Dev, 2020, 191: 111336. doi:10.1016/j.mad.2020.111336.
[5] Miyake MM, Nocera A, Levesque P, et al. Double-blind placebo-controlled randomized clinical trial of verapamil for chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2017, 140(1): 271-273. doi:10.1016/j.jaci.2016.11.014.
[6] de Almeida AS, Bernardes LB, Trevisan G. TRP channels in cancer pain[J]. Eur J Pharmacol, 2021, 904: 174185. doi:10.1016/j.ejphar.2021.174185.
[7] Tang R, Li ZP, Li MX, et al. Pro-inflammatory role of transient receptor potential canonical channel 6 in the pathogenesis of chronic rhinosinusitis with nasal polyps[J]. Int Forum Allergy Rhinol, 2018, 8(11): 1334-1341. doi:10.1002/alr.22208.
[8] Tong XT, Liu PQ, Zhou HQ, et al. The expression and significance of TRPM8 among chronic rhinosinusitis with nasal polyps[J]. Chin J Otorhinolaryngol Head Neck Surg, 2021, 56(10): 1059-1065. doi:10.3760/cma.j.cn115330-20210430-00243.
[9] Tokunaga T, Ninomiya T, Kato Y, et al. The significant expression of TRPV3 in nasal polyps of eosinophilic chronic rhinosinusitis[J]. Allergol Int, 2017, 66(4): 610-616. doi:10.1016/j.alit.2017.04.002.
[10] Tóth E, Tornóczky T, Kneif J, et al. Upregulation of extraneuronal TRPV1 expression in chronic rhinosinusitis with nasal polyps[J]. Rhinology, 2018, 56(3): 245-254. doi:10.4193/Rhin17.108.
[11] Butorac C, Krizova A, Derler I. Review: structure and activation mechanisms of CRAC channels[J]. Adv Exp Med Biol, 2020, 1131: 547-604. doi:10.1007/978-3-030-12457-1_23.
[12] Lin L, Dai F, Chen ZC, et al. The intervention of CRAC channels alleviates inflammatory responses in nasal polyps[J]. Int Arch Allergy Immunol, 2015, 167(4): 270-279. doi:10.1159/000441109.
[13] Lin L, Dai F, Chen ZC, et al. In vitro treatment with 2-APB inhibits the inflammation in nasal polyps[J]. Otolaryngol Head Neck Surg, 2015, 153(3): 461-467. doi:10.1177/0194599815589582.
[14] Cocozza G, Garofalo S, Capitani R, et al. Microglial potassium channels: from homeostasis to neurodegeneration[J]. Biomolecules, 2021, 11(12): 1774. doi:10.3390/biom11121774.
[15] Kim HK, Kim JH, Kim HJ, et al. Role of TWIK-related potassium channel-1 in chronic rhinosinusitis[J]. J Allergy Clin Immunol, 2018, 141(3): 1124-1127.e6. doi:10.1016/j.jaci.2017.10.012.
[16] Kohanski MA, Brown L, Orr M, et al. Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling[J]. Respir Res, 2021, 22(1): 31. doi:10.1186/s12931-021-01631-0.
[17] Mutchler SM, Kirabo A, Kleyman TR. Epithelial sodium channel and salt-sensitive hypertension[J]. Hypertension, 2021, 77(3): 759-767. doi:10.1161/HYPERTENSIONAHA.120.14481.
[18] Jiang YM, Xu J, Chen YQ, et al. Expression and distribution of epithelial sodium channel in nasal polyp and nasal mucosa[J]. Eur Arch Otorhinolaryngol, 2015, 272(11): 3361-3366. doi:10.1007/s00405-014-3477-5.
[19] Yasuda M, Niisato N, Miyazaki H, et al. Epithelial Na+ channel and ion transport in human nasal polyp and paranasal sinus mucosa[J]. Biochem Biophys Res Commun, 2007, 362(3): 753-758. doi:10.1016/j.bbrc.2007.08.065.
[20] Kim JH, Kwon HJ, Jang YJ. Effects of rhinovirus infection on the expression and function of cystic fibrosis transmembrane conductance regulator and epithelial sodium channel in human nasal mucosa[J]. Ann Allergy Asthma Immunol, 2012, 108(3): 182-187. doi:10.1016/j.anai.2011.12.018.
[21] Saber A, Nakka SS, Hussain R, et al. Staphylococcus aureus in chronic rhinosinusitis: the effect on the epithelial chloride channel(cystic fibrosis transmembrane conductance regulator, CFTR)and the epithelial sodium channel(ENaC)physiology[J]. Acta Otolaryngol, 2019, 139(7): 652-658. doi:10.1080/00016489.2019.1603513.
[22] Ba GY, Tang R, Mao S, et al. The expression and regulation of Na+-K+-ATPase in nasal epithelial cells of chronic rhinosinusitis with nasal polyps[J]. ORL J Otorhinolaryngol Relat Spec, 2022, 84(2):139-146. doi:10.1159/000517101.
[23] Liu YN, Liu ZT, Wang KW. The Ca2+-activated chloride channel ANO1/TMEM16A: an emerging therapeutic target for epithelium-originated diseases? [J]. Acta Pharm Sin B, 2021, 11(6): 1412-1433. doi:10.1016/j.apsb.2020.12.003.
[24] Gaurav R, Bewtra AK, Agrawal DK. Chloride channel 3 channels in the activation and migration of human blood eosinophils in allergic asthma[J]. Am J Respir Cell Mol Biol, 2015, 53(2): 235-245. doi:10.1165/rcmb.2014-0300OC.
[25] Li HB, Han DM, Zhou B, et al. Expressions of chloride channel ClC-2 and ClC-3 in human nasal polyps[J]. J Clin Otorhinolaryngol, 2003, 17(5): 266-267.
[26] Li HB, Jiang HY, Cheng L, et al. Possible role of transforming growth factor beta and interleukin-4 in the up-regulation of CLC-2 and CLC-3 in chronic rhinosinusitis[J]. Am J Rhinol, 2007, 21(4): 389-394. doi:10.2500/ajr.2007.21.3045.
[27] Maule G, Ensinck M, Bulcaen M, et al. Rewriting CFTR to cure cystic fibrosis[J]. Prog Mol Biol Transl Sci, 2021, 182: 185-224. doi:10.1016/bs.pmbts.2020.12.018.
[28] Nguyen TN, Do BH, Kitamura T, et al. Expression of Cl- channels/transporters in nasal polyps[J]. Eur Arch Otorhinolaryngol, 2020, 277(8): 2263-2270. doi:10.1007/s00405-020-05981-1.
[29] McCormick J, Hoffman K, Thompson H, et al. Differential chloride secretory capacity in transepithelial ion transport properties in chronic rhinosinusitis[J]. Am J Rhinol Allergy, 2020, 34(6): 830-837. doi:10.1177/1945892420930975.
[30] Beswick DM, Humphries SM, Balkissoon CD, et al. Impact of cystic fibrosis transmembrane conductance regulator therapy on chronic rhinosinusitis and health status: deep learning CT analysis and patient-reported outcomes[J]. Ann Am Thorac Soc, 2022, 19(1): 12-19. doi:10.1513/AnnalsATS.202101-057OC.
[31] Kim HK, Kook JH, Kang KR, et al. Increased expression of hCLCA1 in chronic rhinosinusitis and its contribution to produce MUC5AC[J]. Laryngoscope, 2016, 126(11): E347-E355. doi:10.1002/lary.26109.
[32] Salomon JJ, Albrecht T, Graeber SY, et al. Chronic rhinosinusitis with nasal polyps is associated with impaired TMEM16A-mediated epithelial chloride secretion[J]. J Allergy Clin Immunol, 2021, 147(6): 2191-2201.e2. doi:10.1016/j.jaci.2021.02.008.
[33] Molinari G, Molinari L, Nervo E. Environmental and endogenous acids can trigger allergic-type airway reactions[J]. Int J Environ Res Public Health, 2020, 17(13): E4688. doi:10.3390/ijerph17134688.
[34] Min JY, Ocampo CJ, Stevens WW, et al. Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: possible role of the nongastric H, K-ATPase[J]. J Allergy Clin Immunol, 2017, 139(1): 130-141.e11. doi:10.1016/j.jaci.2016.07.020.
[35] Vullo S, Kellenberger S. A molecular view of the function and pharmacology of acid-sensing ion channels[J]. Pharmacol Res, 2020, 154: 104166. doi:10.1016/j.phrs.2019.02.005.
[36] Tang R, Ba GY, Li MX, et al. Evidence for role of acid-sensing ion channel 1a in chronic rhinosinusitis with nasal polyps[J]. Eur Arch Otorhinolaryngol, 2021, 278(7): 2379-2386. doi:10.1007/s00405-020-06521-7.
[37] Cai XY, Yao Y, Teng F, et al. The role of P2X7 receptor in infection and metabolism: based on inflammation and immunity[J]. Int Immunopharmacol, 2021, 101(Pt A): 108297. doi:10.1016/j.intimp.2021.108297.
[38] Wang Y, Chen S, Wang WW, et al. Role of P2X7R in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps[J]. Mol Med Rep, 2021, 24: 521. doi:10.3892/mmr.2021.12160.
[39] 李春花, 刘肖, 刘红兵. 半乳糖凝集素10与慢性鼻窦炎伴鼻息肉[J]. 山东大学耳鼻喉眼学报, 2021, 35(3): 106-111. doi:10.6040/j.issn.1673-3770.0.2020.163. LI Chunhua, LIU Xiao, LIU Hongbing. Galectin-10 and chronic rhinosinusitis with nasal polyps[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(3): 106-111.doi:10.6040/j.issn.1673-3770.0.2020.163.
[40] 康雪, 叶菁. 紧密连接与慢性鼻-鼻窦炎发病机制的研究进展[J]. 山东大学耳鼻喉眼学报, 2017, 31(2): 112-115. doi:10.6040/j.issn.1673-3770.0.2017.042. KANG Xue, YE Jing. Progress of tight junctions and chronic rhinosinusitis[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2017, 31(2): 112-115.doi:10.6040/j.issn.1673-3770.0.2017.042.
[1] WANG Min, LIU Hao, JIANG Luhan, TAN Liyue, LI Wen, FU Xiaolong. Packaging of AAV-ie-Tnfaip8l2 and its effect on improving auditory function in Tnfaip8l2-/- mice [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 7-15.
[2] LI Shiyun, XIE Yan, PAN Jiayu, CHEN Meixin, LONG Dan, ZHANG Chunlin. Meta analysis of clinical efficacy of cochlear implant in elderly patients with postlingual deafness [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 20-30.
[3] FENG Sicong, YU Xiaolan, LOU Dan. Evaluation of the effect of Messerklinger middle turbinate plasty on chronic rhinosinusitis with nasal polyps based on the expression of Ki67 and GM-CSF in vesicular tissue [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 31-39.
[4] LIN Xiaoxue, LIN Baorui, LI Peishan, LU Biaoqing. Application of electronic nasopharyngoscopy combined with narrow band imaging in traditional Chinese medicine syndrome differentiation of nasopharyngeal carcinoma [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 40-46.
[5] LYU Dan, LI Ruzhen, LIU Mingqiu, MENG Xinyu, LI Junyi. Incidence and correlation of anxiety, depression, and sleep disorders in patients with different types of benign paroxysmal positional vertigo [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 62-67.
[6] ZHAO Chunrong, YANG Sen, LI Chunyan, WANG Donghai, YANG Yu, YANG Xiaoying. Effects of continuous positive airway pressure on olfactory and cognitive functions in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 68-73.
[7] XU Juan, CUI Biao, HUANG Jianping, CHEN Yibiao, SHI Jianfei, WANG Yanwen, LIU Zanhua, ZHANG Jianwei. Clinical application of FEES-based swallowing function assessment in elderly patients with pulmonary infections [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 74-79.
[8] WANG Zhiyuan, HAO Zhongkai, ZHANG Chenming. The effect of local micro-pressure oxygen on the repair and oxidative stress of rabbit corneal epithelial cells after injury [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 80-86.
[9] ZHOU Guimei, GUAN Qi, YANG Rong, DAN Yang, LI Jianhong, LIU Peng, XIONG Xinying, LI Xue, TAN Yunqi, LIAO Xuan. Comparison of subjective refraction results between monocular fogging and binocular simultaneous fogging [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 87-91.
[10] WANG Menghui, LI Ao, WEI Hao, JIANG Yue, WU Xingguang, LI Luxi, QIAN Xiaoyun. Multiple mechanisms and clinical warning signs of deafness caused by hepatitis B virus [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(3): 110-114.
[11] WU Fulian, JI Xuying. Layer-specific response distribution characteristics of binaural integration neurons in the auditory cortex and synaptic input regulation mechanism [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 7-17.
[12] WANG Kaijian, WANG Wei, CHEN Xuesheng, FAN Chunsun, HE Yingying, HUANG Dongling, QIAN Cunhui, DING Shujun. Correlation between neutrophil-to-lymphocyte ratio with hearing loss and audiometric thresholds in adults: a cross-sectional study based on NHANES [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 18-28.
[13] ZHAI Xuechun, BIAN Xin, CHEN Jingcai, DENG Jiayu, YE Zi, YANG Pingli. Characteristics and influencing factors of anxiety and depression in patients with chronic frontal sinusitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 35-43.
[14] WANG Xinmeng, JI Junya, YU Haonan, FU Hongchen, WANG Xiang, ZHENG Zekun, LI Yan, ZHONG Yingying. Analysis of refractive prediction accuracy after phacoemulsification combined with goniosynechialysis in acute Angle closure glaucoma [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 74-79.
[15] GAO Qige, ZHANG Hua. Treatment of pulsatile tinnitus: a literature review [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 95-101.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!