Downregulation of caveolin-1 in chronic rhinosinusitis with and without nasal polyps
Hai Lin1, Dong Lin, Xi-Sheng Xiong
1Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, 83 Fenyang Road, Xuhui District, Shanghai, 200031, China.
Abstract:
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.
Insights
Chronic rhinosinusitis (CRS) shows reduced caveolin-1 (Cav-1) expression, impairing its role in host defense. This downregulation in CRS, particularly with nasal polyps, leads to increased cyclin D1 and eNOS levels.
Area of Science:
- Immunology
- Molecular Biology
- Otorhinolaryngology
Background:
- Chronic rhinosinusitis (CRS) pathogenesis is not fully understood.
- Caveolin-1 (Cav-1) is a protein involved in host defense and tumor suppression.
- The role of Cav-1 in CRS requires further investigation.
Purpose of the Study:
- To investigate the expression and function of Cav-1 in patients with CRS.
- To determine the relationship between Cav-1, cyclin D1, and endothelial nitric oxide-synthase (eNOS) in CRS.
- To explore the regulatory effects of cytokines on Cav-1 expression in CRS.
Main Methods:
- Immunohistochemistry to assess Cav-1 protein expression.
- Real-time polymerase chain reaction (PCR) for mRNA analysis of Cav-1, cyclin D1, and eNOS.
- Nasal explant cultures to evaluate Cav-1 response to cytokine stimulation.
Main Results:
- Reduced Cav-1 protein and mRNA expression observed in CRS, especially in CRS with nasal polyps (CRSwNP).
- Elevated mRNA levels of cyclin D1 and eNOS found in CRS patients.
- Cav-1 expression negatively correlated with cyclin D1 and eNOS expression.
- IFN-γ augmented Cav-1 mRNA, while IL-4 and IL-1β suppressed it.
Conclusions:
- Cav-1 expression is downregulated in CRS, particularly in CRSwNP.
- Impaired Cav-1 function contributes to CRS by attenuating inhibition of cyclin D1 and eNOS.
- Overexpression of cyclin D1 and eNOS is a consequence of Cav-1 downregulation in CRS.
- IFN-γ appears crucial for maintaining Cav-1 gene expression.
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