Division of Clinical Immunology and Allergy, Department of Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 s. 3207, Sao Paulo, SP, 01246-000, Brazil.
Laboratory of Immunology, Instituto do Coração (Incor) Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP, Brazil.
Eur Arch Otorhinolaryngol. 2019 Nov;276(11):3247-3249. doi: 10.1007/s00405-019-05581-8. Epub 2019 Jul 30.
The pathogenesis of persistent allergic rhinitis with chronic and refractory nasal obstruction is still unknown. Inflammation and tissue remodeling are known to play a role, but this has not been studied thoroughly. The purpose of this study is to identify the profile of gene expression of inflammatory and remodeling markers in nasal mucosa of patients with PAR and chronic obstruction.
After informed consent, we obtained nasal mucosa tissue from five aeroallergen-sensitized PAR patients undergoing anterior turbinectomy, and control non-sensitized individuals undergoing cerebrospinal fluid fistula repair or rhinoplasty. We assessed the expression of 34 genes related to inflammation and tissue remodeling using the real-time polymerase chain reaction (qPCR) to quantify each mRNA.
IL-4 mRNA was upregulated in nasal mucosa of all five patients; CCR3, CCR8 and Eotaxin-2 were upregulated in four out of five patient samples; while IL-5 and IL-13 were upregulated in two of them. TGF-β1 was not upregulated in PAR samples. mRNA from metalloproteinases MMP-7, MMP13 and MMP15 were upregulated in three out of five samples. Our results indicate a typical mRNA expression profile of the infiltrating inflammatory Th2 cells and eosinophils, combined with altered gene expression of remodeling-related proteins in stromal cells from the mucosa.
Prolonged allergen challenge can lead to persistent upregulation of genes for inflammatory mediators such as IL-4 Th2/eosinophil cytokines, chemokines and receptors, which may play an important role in maintaining PAR with chronic nasal obstruction. Our findings may have therapeutic implications, including the use of anti-IL4, -CCR3 or -MMP therapy to ameliorate the condition.
持续性变应性鼻炎伴慢性和难治性鼻阻塞的发病机制尚不清楚。已知炎症和组织重塑起作用，但这尚未得到深入研究。本研究旨在确定变应性鼻炎伴慢性阻塞患者鼻黏膜炎症和重塑标志物的基因表达谱。
在获得知情同意后，我们从前庭神经切除术的 5 名变应原致敏 PAR 患者和行脑脊液瘘修补术或鼻整形术的非致敏对照个体中获得鼻黏膜组织。我们使用实时聚合酶链反应（qPCR）评估与炎症和组织重塑相关的 34 个基因的表达，以定量每种 mRNA。
所有 5 名患者的鼻黏膜中 IL-4 mRNA 上调；4 名患者中有 5 名 CCR3、CCR8 和 Eotaxin-2 上调；2 名患者中有 IL-5 和 IL-13 上调。TGF-β1 在 PAR 样本中未上调。基质细胞中 MMP-7、MMP13 和 MMP15 的 mRNA 上调了 3 个样本。我们的结果表明，浸润性 Th2 细胞和嗜酸性粒细胞的典型 mRNA 表达谱，以及黏膜基质细胞中重塑相关蛋白的基因表达改变。
长时间的过敏原刺激可导致炎症介质基因如 IL-4 Th2/嗜酸性粒细胞细胞因子、趋化因子和受体持续上调，这可能在维持伴有慢性鼻阻塞的 PAR 中起重要作用。我们的发现可能具有治疗意义，包括使用抗 IL-4、-CCR3 或-MMP 治疗来改善病情。
