Abstract
Both up- and down-regulation of the Toll-like receptors (TLRs) and antimicrobial peptides (AMPs) of the sinonasal mucosa have already been associated with the pathogenesis of chronic rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyps. The objective of this study was to determine the expression of all known TLR and several AMP genes and some selected proteins in association with allergy, asthma and aspirin intolerance (ASA) in CRS subgroups. RT-PCR was applied to measure the mRNA expressions of 10 TLRs, four defensins, lysozyme, cathelicidin and lactoferrin (LTF) in sinonasal samples from patients with CRSsNP (n = 19), CRSwNP [ASA(−): 17; ASA(+): 7] and in control subjects (n = 12). Protein expressions were detected with immunohistochemistry (n = 10). Statistical analysis was done with the Kruskal-Wallis ANOVA, Mann-Whitney U, and Student t test. TLR2, TLR5, TLR6, TLR7, TLR8, TLR9, β-defensins 1 and 4, cathelicidin and LTF mRNA expressions were significantly (p < 0.05) increased in CRSwNP, whereas only TLR2 and LTF were up-regulated in CRSsNP compared to controls. There was no statistical difference in respect of allergy, aspirin intolerance and smoking between CRSsNP, ASA(−) and ASA(+) CRSwNP patients. TLR2, TLR3, TLR4, LTF, β defensin 2 and lysozyme protein expressions were found to be elevated in macrophages of CRSwNP samples (p < 0.05). Gene expression analysis showed markedly different expressions in CRSwNP (6 out of 10 TLR and 4 out of 7 AMP genes were up-regulated) compared to CRSsNP (1/10, 1/7). The distinct activation of the innate immunity may support the concept that CRSsNP and CRSwNP are different subtypes of CRS. These findings were found to be independent from allergy, asthma, smoking, aspirin intolerance and systemic steroid application.
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Acknowledgments
The study was supported by a Jedlik Anyos grant; NKFP-07-A1-ORLPOLYP-hu; OM-00034/2008. The authors gratefully thank for Eva Viharos for the statistical analyses.
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This study was supported by Jedlik Anyos Grant; NKFP-07-A1-ORLPOLYP-hu; OM-00034/2008. The study was approved by the local and national ethics committees (IRB: Health Science Council, Scientific and Ethics Board, ETT-TUKEB). Informed consent was obtained from all individual participants included in the study.
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Hirschberg, A., Kiss, M., Kadocsa, E. et al. Different activations of toll-like receptors and antimicrobial peptides in chronic rhinosinusitis with or without nasal polyposis. Eur Arch Otorhinolaryngol 273, 1779–1788 (2016). https://doi.org/10.1007/s00405-015-3816-1
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DOI: https://doi.org/10.1007/s00405-015-3816-1