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Increased expression of IL-19 in the epithelium of patients with chronic rhinosinusitis and nasal polyps

机译:慢性鼻鼻窦炎和鼻息肉患者上皮中IL-19的表达增加

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Background: Chronic rhinosinusitis (CRS) is an inflammation of the nose and of the paranasal sinuses. The involvement of the respiratory epithelium in the mechanisms of CRS is poorly understood. Aims: Among proteins expressed by nasal epithelial cells in CRS, IL-19 may have key functions. We here aimed to determine the expression and regulation of IL-19. Methods: Nasal biopsies from normal subjects (n = 12), subjects with CRS but without nasal polyps (NP) (CRSsNP, n = 12) and with CRS with NP (CRSwNP, n = 15) were collected. Human Asthma Gene Array and real-time PCR were used to evaluate gene expression, western blot analysis and immunohistochemistry for protein expression. Results for IL-19 were confirmed by real-time PCR. The constitutive and stimulated (LPS, TGF β) expression of IL-19 and cell proliferation were evaluated in a nasal epithelial cell line (RPMI 2650). Results: Human Asthma Gene Array showed an increased IL-19 gene expression in NP from patients with CRS in comparison with normal subjects. Real-time PCR confirmed the IL-19 mRNA up-regulation in patients with CRSwNP and showed an up-regulation of IL-19, at lower extent, in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) in comparison with normal subjects. Western blot analysis confirmed that IL-19 is increased also at protein level in patients with CRSwNP in comparison with normal subjects. In NP, IL-19 is highly expressed in the metaplastic nasal epithelium when compared to normal or hyperplastic epithelium. LPS stimulation increased IL-19 expression, and recombinant IL-19 increased cell proliferation in nasal epithelial cells. Conclusions: IL-19 is overexpressed in the epithelium in CRSwNP and increases epithelial cell proliferation.
机译:背景:慢性鼻-鼻窦炎(CRS)是鼻子和鼻旁窦的炎症。呼吸上皮细胞参与CRS的机制了解甚少。目的:在CRS鼻上皮细胞表达的蛋白质中,IL-19可能具有关键功能。我们在这里旨在确定IL-19的表达和调控。方法:从正常受试者(n = 12),患有CRS但无鼻息肉(NP)的受试者(CRSsNP,n = 12)和具有NP的CRS(CRSwNP,n = 15)受试者进行鼻活检。使用人类哮喘基因阵列和实时PCR评估基因表达,蛋白质印迹分析和免疫组织化学检测蛋白质表达。 IL-19的结果通过实时PCR确认。在鼻上皮细胞系(RPMI 2650)中评估IL-19的组成型和刺激性(LPS,TGFβ)表达以及细胞增殖。结果:与正常人相比,人哮喘基因阵列显示CRS患者NP中IL-19基因表达增加。实时PCR证实CRSwNP患者的IL-19 mRNA上调,与无正常鼻息肉的慢性鼻鼻窦炎(CRSsNP)患者相比,IL-19的表达水平较低。蛋白质印迹分析证实,与正常受试者相比,CRSwNP患者的IL-19水平也在蛋白质水平上增加。在NP中,与正常或增生上皮相比,IL-19在化生性鼻上皮中高表达。 LPS刺激增加了IL-19的表达,重组IL-19增强了鼻上皮细胞的细胞增殖。结论:IL-19在CRSwNP的上皮细胞中过度表达,并增加上皮细胞的增殖。

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