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Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta

Published online by Cambridge University Press:  15 June 2015

N T Phan*
Affiliation:
School of Pharmacy, University of Queensland, Brisbane, Australia Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, Australia
P J Cabot
Affiliation:
School of Pharmacy, University of Queensland, Brisbane, Australia
B D Wallwork
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia
A U Cervin
Affiliation:
School of Medicine, University of Queensland, Brisbane, Australia Department of Otolaryngology, Head and Neck Surgery, Royal Brisbane and Women's Hospital, Australia
B J Panizza
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia
*
Address for correspondence: Dr Nga T Phan, Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, QLD 4120, Australia Fax: (07) 3394 2263 E-mail: nth_phan@yahoo.com.au

Abstract

Background:

Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling.

Objective:

This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

Type
Review Articles
Copyright
Copyright © JLO (1984) Limited 2015 

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References

1Aukema, A, Fokkens, W. Chronic rhinosinusitis: management for optimal outcomes. Treat Respir Med 2004;3:97105CrossRefGoogle ScholarPubMed
2Daines, S, Orlandi, R. Chronic rhinosinusitis. Facial Plast Surg Clin North Am 2012;20:110CrossRefGoogle ScholarPubMed
3Goldenberg, D, Goldstein, B, eds. Handbook of Otolaryngology: Head and Neck Surgery. New York: Thieme Medical Publishers, 2011Google Scholar
4Fokkens, W, Lund, V, Mullol, J, Bachert, C, Alobid, I, Baroody, F et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology 2012;50:112CrossRefGoogle ScholarPubMed
5Meltzer, E, Hamilos, D. Rhinosinusitis diagnosis and management for the clinician: a synopsis of recent consensus guidelines. Mayo Clin Proc 2011;86:427–43CrossRefGoogle ScholarPubMed
6Lee, S, Lane, A. Chronic rhinosinusitis as a multifactorial inflammatory disorder. Curr Infect Dis Rep 2011;13:159–68CrossRefGoogle ScholarPubMed
7van Agthoven, M, Fokkens, W, van de Merwe, J, Marijke van Bolhuis, E, Uyl-de Groot, C, Busschbach, J. Quality of life of patients with refractory chronic rhinosinusitis: effects of filgrastim treatment. Am J Rhinol 2001;15:231–7CrossRefGoogle ScholarPubMed
8Australian Institute of Health and Welfare. Asthma, Chronic Obstructive Pulmonary Disease and Other Respiratory Diseases in Australia. Canberra: Australian Institute of Health and Welfare, 2010Google Scholar
9Zhang, Q, Wang, C, Han, D, Sy, C, Huang, Q, Sun, Y et al. Differential expression of toll-like receptor pathway genes in chronic rhinosinusitis with or without nasal polyps. Acta Otolaryngol 2013;133:165–73CrossRefGoogle ScholarPubMed
10Ponikau, J, Sherris, D, Kern, E, Homburger, H, Frigas, E, Gaffey, T et al. The diagnosis and incidence of allergic fungal sinusitis. Mayo Clin Proc 1999;74:877–84CrossRefGoogle ScholarPubMed
11Bachert, C, Gevaert, P, Van Cauwenberge, P. Staphylococcus aureus superantigens and airway disease. Curr Allergy Asthma Rep 2002;2:252–8CrossRefGoogle ScholarPubMed
12Bachert, C, Watelet, J, Gevaert, P, Van Cauwenberge, P. Pharmacological management of nasal polyposis. Drugs 2005;65:1537–52CrossRefGoogle ScholarPubMed
13Akdis, C, Bachert, C, Cingi, C, Dykewicz, M, Hellings, P, Naclerio, R et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 2013;131:1479–90CrossRefGoogle ScholarPubMed
14Eloy, P, Poirrier, A, De Dorlodot, C, Van Zele, T, Watelet, J, Bertrand, B. Actual concepts in rhinosinusitis: a review of clinical presentations, inflammatory pathways, cytokine profiles, remodelling, and management. Curr Allergy Asthma Rep 2011;11:146–62CrossRefGoogle ScholarPubMed
15Daines, S, Orlandi, R. Inflammatory cytokines. Curr Opin Otolaryngol Head Neck Surg 2010;18:187–90CrossRefGoogle ScholarPubMed
16Kumar, V, Abbas, A, Aster, J.Robbins Basic Pathology, 9th edn.Philadelphia: Elsevier Saunders, 2013Google Scholar
17Derycke, L, Eyerich, S, Van Crombruggen, K, Perez-Novo, C, Holtappels, G, Deruyck, N et al. Mixed T helper cell signatures in chronic rhinosinusitis with and without polyps. PLoS One 2014;9:e97581CrossRefGoogle ScholarPubMed
18Ramanathan, M, Lane, A. Innate immunity of the sinonasal cavity and its role in chronic rhinosinusitis. Otolaryngol Head Neck Surg 2007;136:348–56CrossRefGoogle ScholarPubMed
19Riechelmann, H, Deutschle, T, Rozsasi, A, Keck, T, Polzehl, D, Burner, H. Nasal biomarker profiles in acute and chronic rhinosinusitis. Clin Exp Allergy 2005;35:1186–91CrossRefGoogle ScholarPubMed
20Bachert, C, Wagenmann, M, Hauser, U, Rudack, C. IL-5 synthesis is upregulated in human nasal polyp tissue. J Allergy Clin Immunol 1997;99:837–42CrossRefGoogle ScholarPubMed
21Lawrence, T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol 2009;1:a001651CrossRefGoogle ScholarPubMed
22Akira, S, Uematsu, S, Takeuchi, O. Pathogen recognition and innate immunity. Cell 2006;124:783801CrossRefGoogle ScholarPubMed
23Ghosh, S, Karin, M. Missing pieces in the NF-kappaB puzzle. Cell 2002;109:8196CrossRefGoogle ScholarPubMed
24Strnad, J, Burke, J. IkappaB kinase inhibitors for treating autoimmune and inflammatory disorders: potential and challenges. Trends Pharmacol Sci 2007;28:142–8CrossRefGoogle ScholarPubMed
25Karin, M, Ben-Neriah, Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 2000;18:621–63CrossRefGoogle Scholar
26Senftleben, U, Cao, Y, Xiao, G, Greten, F, Krahn, G, Bonizzi, G et al. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signalling pathway. Science 2001;293:1495–9CrossRefGoogle Scholar
27Bonizzi, G, Karin, M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004;25:280–8CrossRefGoogle ScholarPubMed
28Novack, D, Yin, L, Hagen-Stapleton, A, Schreiber, R, Goeddel, D, Ross, F et al. The IkappaB function of NF-kappaB2 p100 controls stimulated osteoclastogenesis. J Exp Med 2003;198:771–81CrossRefGoogle ScholarPubMed
29Zandi, E, Rothwarf, D, Delhase, M, Hayakawa, M, Karin, M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell 1997;91:243–52CrossRefGoogle ScholarPubMed
30Hoesel, B, Schmid, J. The complexity of NF-κB signalling in inflammation and cancer. Mol Cancer 2013;12:115CrossRefGoogle ScholarPubMed
31Fraczek, M, Rostkowska-Nadolska, B, Kapral, M, Szota, J, Krecicki, T, Mazurek, U. Microassay analysis of NF-κB-dependent genes in chronic rhinosinusitis with nasal polyps. Adv Clin Exp Med 2013;22:209–17Google Scholar
32Takeno, S, Hirakawa, K, Ueda, T, Furukido, K, Osada, R, Yajin, K. Nuclear factor-kappa B activation in the nasal polyp epithelium: relationship to local cytokine gene expression. Laryngoscope 2002;112:53–8CrossRefGoogle ScholarPubMed
33Yang, L, Cohn, L, Zhang, D, Homer, R, Ray, A, Ray, P. Essential role of nuclear factor kappaB in the induction of eosinophils in allergic airway inflammation. J Exp Med 1998;188:1739–50CrossRefGoogle ScholarPubMed
34Wang, Z, Zhang, Q, Li, Y, Li, P, Zhang, G, Li, Y. Involvement of mitogen-activated protein kinases and nuclear factor kappa B pathways in signalling COX-2 expression in chronic rhinosinusitis. Inflamm Res 2009;58:649–58CrossRefGoogle ScholarPubMed
35Zhang, H, Ching, S, Chen, Q, Li, Q, An, Y, Quan, N. Localised inflammation in peripheral tissue signals the CNS for sickness response in the absence of interleukin-1 and cyclooxygenase-2 in the blood and brain. Neuroscience 2008;157:895907CrossRefGoogle ScholarPubMed
36Yano, M, Matsumura, T, Senokuchi, T, Ishii, N, Murata, Y, Taketa et al. Statins activate peroxisome proliferator-activated receptor gamma through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages. Circ Res 2007;100:1442–51CrossRefGoogle ScholarPubMed
37Duggan, S, Lindstrom, T, Iglesias, T, Bennett, P, Mann, G, Bartlett, S. Role of atypical protein kinase C isozymes and NF-kappaB in IL-1beta-induced expression of cyclooxygenase-2 in human myometrial smooth muscle cells. J Cell Physiol 2007;210:637–43CrossRefGoogle ScholarPubMed
38Zhou, H, Shin, E, Guo, L, Youn, U, Bae, K, Kang, S et al. Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB, JNK and p38 MAPK inactivation. Eur J Pharmacol 2008;586:340–9CrossRefGoogle ScholarPubMed
39Tomassen, P, Van Zele, T, Zhang, N, Perez-Novo, C, Van Bruaene, N, Gevaert, P et al. Pathophysiology of chronic rhinosinusitis. Proc Am Thorac Soc 2011;8:115–20CrossRefGoogle ScholarPubMed
40Van Crombruggen, K, Zhang, N, Gevaert, P, Tomassen, P, Bachert, C. Pathogenesis of chronic rhinosinusitis: inflammation. J Allergy Clin Immunol 2011;128:728–32CrossRefGoogle ScholarPubMed
41Van Bruaene, N, Derycke, L, Perez-Novo, C, Gevaert, P, Holtappels, G, De Ruyck, N et al. TGF-beta signalling and collagen deposition in chronic rhinosinusitis. J Allergy Clin Immunol 2009;124:253–9CrossRefGoogle ScholarPubMed
42Yang, Y, Zhang, N, Van Crombruggen, K, Hu, G, Hong, S, Bachert, C. Transforming growth factor-beta1 in inflammatory airway disease: a key for understanding inflammation and remodelling. Allergy 2012;67:1193–202CrossRefGoogle Scholar
43Spinozzi, F, de Benedictis, D, de Benedictis, F. Apoptosis, airway inflammation and anti-asthma therapy: from immunobiology to clinical application. Pediatr Allergy Immunol 2008;19:287–95CrossRefGoogle ScholarPubMed
44Leask, A, Abraham, D. TGF-beta signalling and the fibrotic response. FASEB J 2004;18:816–27CrossRefGoogle ScholarPubMed
45Gevaert, P, Van Bruaene, N, Cattaert, T, Van Steen, K, Van Zele, T, Acke, F et al. Mepolizumab, a humanised anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol 2011;128:989–95CrossRefGoogle Scholar
46Van Bruaene, N, Bachert, C. Tissue remodelling in chronic rhinosinusitis. Curr Opin Allergy Clin Immunol 2011;11:811CrossRefGoogle ScholarPubMed
47Amini-Vaughan, Z, Martinez-Moczygemba, M, Huston, D. Therapeutic strategies for harnessing human eosinophils in allergic inflammation, hypereosinophilic disorders and cancer. Curr Allergy Asthma Rep 2012;12:402–12CrossRefGoogle ScholarPubMed
48Valera, F, Umezawa, K, Brassesco, M, Castro-Gamero, A, Queiroz, R, Scrideli, C et al. Suppression of inflammatory cytokine secretion by an NF-κB inhibitor DHMEQ in nasal polyps fibroblasts. Cell Physiol Biochem 2012;30:1322CrossRefGoogle ScholarPubMed
49Kou, W, Hu, G, Yao, H, Wang, X, Shen, Y, Kang, H et al. Regulation of transforming growth factor-β1 activation and expression in the tissue remodelling involved in chronic rhinosinusitis. ORL J Otorhinolaryngol Relat Spec 2012;74:172–8CrossRefGoogle ScholarPubMed
50Meltzer, E, Hamilos, D, Hadley, J, Lanza, D, Marple, B, Nicklas, R et al. Rhinosinusitis: establishing definitions for clinical research and patient care. Otolaryngol Head Neck Surg 2004;131(6 suppl):S162CrossRefGoogle ScholarPubMed
51Serpero, L, Petecchia, L, Sabatini, F, Giuliani, M, Silvestri, M, Di Blasi, P et al. The effect of transforming growth factor (TGF)-beta1 and (TGF)-beta2 on nasal polyp fibroblast activities involved upper airway remodelling: modulation by fluticasone propionate. Immunol Lett 2006;105:61–7CrossRefGoogle ScholarPubMed
52Wallwork, B, Coman, W, Mackay-Sim, A, Cervin, A. Effect of clarithromycin on nuclear factor-kappa B and transforming growth factor-beta in chronic rhinosinusitis. Laryngoscope 2004;114:286–90CrossRefGoogle ScholarPubMed