Hirschberg Andor, Kiss Maria, Kadocsa Edit, Polyanka Hilda, Szabo Kornelia, Razga Zsolt, Bella Zsolt, Tiszlavicz Laszlo, Kemeny Lajos
Department of Oto-Rhino-Laryngology, St John's Hospital, Dios arok 1-3, 1125, Budapest, Hungary.
Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
Eur Arch Otorhinolaryngol. 2016 Jul;273(7):1779-88. doi: 10.1007/s00405-015-3816-1. Epub 2015 Oct 30.
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.
鼻黏膜中Toll样受体（TLRs）和抗菌肽（AMPs）的上调和下调均已与伴有（CRSwNP）或不伴有（CRSsNP）鼻息肉的慢性鼻窦炎的发病机制相关。本研究的目的是确定所有已知TLR和几种AMP基因以及一些选定蛋白质在CRS亚组中与过敏、哮喘和阿司匹林不耐受（ASA）相关的表达情况。应用逆转录聚合酶链反应（RT-PCR）来测量来自CRSsNP患者（n = 19）、CRSwNP患者[ASA（-）：17例；ASA（+）：7例]以及对照受试者（n = 12）的鼻窦样本中10种TLR、4种防御素、溶菌酶、cathelicidin和乳铁蛋白（LTF）的mRNA表达。采用免疫组织化学法检测蛋白质表达（n = 10）。采用Kruskal-Wallis方差分析、Mann-Whitney U检验和Student t检验进行统计分析。与对照组相比，CRSwNP中TLR2、TLR5、TLR6、TLR7、TLR8、TLR9、β-防御素1和4、cathelicidin和LTF的mRNA表达显著升高（p < 0.05），而CRSsNP中仅TLR2和LTF上调。CRSsNP、ASA（-）和ASA（+）CRSwNP患者在过敏、阿司匹林不耐受和吸烟方面无统计学差异。发现CRSwNP样本的巨噬细胞中TLR2、TLR3、TLR4、LTF、β-防御素2和溶菌酶的蛋白质表达升高（p < 0.05）。基因表达分析显示，与CRSsNP（1/10，1/7）相比，CRSwNP中存在明显不同的表达（10种TLR中的6种和7种AMP基因中的4种上调）。固有免疫的明显激活可能支持CRSsNP和CRSwNP是CRS不同亚型的概念。这些发现与过敏、哮喘、吸烟、阿司匹林不耐受和全身应用类固醇无关。
