Lin Hai, Lin Dong, Xiong Xi-Sheng, Dai Xiong-Xiong, Lin Ting
Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, 83 Fenyang Road, Xuhui District, Shanghai, 200031, China.
Eur Arch Otorhinolaryngol. 2015 Mar;272(3):613-8. doi: 10.1007/s00405-014-3146-8. Epub 2014 Jun 19.
The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial. Recent evidence has suggested that caveolin-1 (Cav-1) is a 22 kDa scaffolding protein and plays a pivotal role in host defense against infections and tumour suppression by reducing production of cyclin D1 and endothelial nitric oxide-synthase (eNOS). However, little is known about their roles in CRS. Therefore, we aimed to investigate the expression and role of Cav-1 in CRS. Cav-1 protein expression were investigated by immunohistochemistry method and mRNA expression of Cav-1, cyclin D1 and eNOS were assessed by real-time polymerase chain reaction in CRS and control subjects. Moreover, the effects of various stimulators with different concentrations and time on Cav-1 were evaluated on nasal explant culture. The results showed that weaker expression of Cav-1 protein and mRNA were observed in CRS, especially in CRS with nasal polyps (CRSwNP), stronger mRNA expression of cyclin D1 and eNOS were observed in CRS and Cav-1 expression was negatively related to cyclin D1 and eNOS expression, respectively. Cav-1 mRNA was augmented by IFN-γ, but supressed by IL-4 and IL-1β. In conclusion, the expression of Cav-1 was downregulated in CRS and the role of Cav-1 was impaired in CRS, especially in CRSwNP, leading to the attenuation of inhibition effect on cyclin D1 and eNOS and resulted in the overexpression of cyclin D1 and eNOS. IFN-γ may be essential for Cav-1 gene expression.
人类慢性鼻-鼻窦炎(CRS)的发病机制仍存在争议。最近的证据表明,小窝蛋白-1(Cav-1)是一种22 kDa的支架蛋白,通过减少细胞周期蛋白D1和内皮型一氧化氮合酶(eNOS)的产生,在宿主抗感染防御和肿瘤抑制中起关键作用。然而,它们在CRS中的作用尚不清楚。因此,我们旨在研究Cav-1在CRS中的表达及作用。采用免疫组织化学方法检测Cav-1蛋白表达,通过实时聚合酶链反应评估CRS患者和对照者中Cav-1、细胞周期蛋白D1和eNOS的mRNA表达。此外,在鼻外植体培养中评估不同浓度和时间的各种刺激物对Cav-1的影响。结果显示,CRS患者中观察到Cav-1蛋白和mRNA表达较弱,尤其是在伴有鼻息肉的CRS(CRSwNP)中;CRS患者中观察到细胞周期蛋白D1和eNOS的mRNA表达较强,且Cav-1表达分别与细胞周期蛋白D1和eNOS表达呈负相关。IFN-γ可增加Cav-1 mRNA表达,但IL-4和IL-1β可抑制其表达。总之,CRS中Cav-1表达下调,其作用受损,尤其是在CRSwNP中,导致对细胞周期蛋白D1和eNOS的抑制作用减弱,从而导致细胞周期蛋白D1和eNOS过表达。IFN-γ可能对Cav-1基因表达至关重要。