Different activation of toll-like receptors and antimicrobial peptides in chronic rhinosinusitis with or without nasal polyposis

Hirschberg, Andor and Kiss, Mária and Kadocsa, Edit and Polyánka, Hilda and Szabó, Kornélia and Rázga, Zsolt and Bella, Zsolt and Tiszlavicz, László and Kemény, Lajos (2016) Different activation of toll-like receptors and antimicrobial peptides in chronic rhinosinusitis with or without nasal polyposis. European Archives of Oto-Rhino-Laryngology, 273 (7). pp. 1779-1788. ISSN 0937-4477

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Abstract

Background: 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. Objective: Determination of 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. Methods: Patients with CRSsNP (n=19), CRSwNP (ASA[-]:17; ASA[+]:7) and control subjects (n=12) were selected. Sinonasal samples were taken during endonasal surgery and RT-PCR was used to measure mRNA expressions of 10 TLRs, 4 defesins, lysozyme, cathelicidin and lactoferrin (LTF). In several cases immunohistochemistry was performed to evaluate protein expressions. Statistical analysis was done with the Kruskall-Wallis ANOVA, Mann-Whitney U and Student-t-test. Results: 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 expression was found to be increased in CRSwNP stainings (p<0.05) dominantly in macrophages. Conclusions: 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 endotypes of CRS. These findings were found to be independent from allergy, asthma, smoking, aspirin intolerance and systemic steroid application.

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