ABSTRACT
BACKGROUND: The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial. Recent evidence has suggested that interleukin (IL)-9 is vital in eliciting inflammatory response, stimulating cell proliferation and preventing apoptosis, through binding to the IL-9 receptor (IL-9R). However, little is known about the roles of both molecules in the etiology of CRS. Therefore, this study aimed to assess IL-9 and IL-9R expression and determine their roles in the pathophysiology of CRS. METHODS: Immunohistochemistry was used to assess IL-9 and IL-9R immunolabeling. In addition, Western blotting and real-time polymerase chain reaction (PCR) were used for IL-9 and IL-9R protein and mRNA level quantitation, respectively, in CRS and control subjects. Furthermore, the effects of various stimulators at different concentrations and time on IL-9 were evaluated using nasal explant cultures. RESULTS: IL-9 and IL-9R were overexpressed in CRS, especially in CRS with nasal polyps. Interestingly, IL-9 expression was closely related to that of IL-9R. In addition, IL-9 mRNA levels were increased by treatment with IL-4, IL-17A, IL-1beta, and the IL-4 and transforming growth factor (TGF) beta1 combination, but suppressed by interferon gamma and IL-27. CONCLUSION: IL-9 and IL-9R were overexpressed in CRS at both protein and mRNA levels. In addition, IL-4, IL-17A, IL-1beta, and the IL-4 and TGF-beta1 combination contributed to increased IL-9 levels. Our findings indicate that IL-9 may play a proinflammatory role after IL-9R binding to induce mucosal epithelial cell growth, gland epithelial cell proliferation, and inflammatory cell infiltration in CRS. Future studies are required to further define the role of IL-9 in CRS etiology.
Subject(s)
Interleukin-9/analysis , Rhinitis/immunology , Sinusitis/immunology , Adolescent , Adult , Aged , Chronic Disease , Female , Humans , Immunohistochemistry , Interleukin-9/genetics , Male , Middle Aged , Nasal Mucosa/immunology , RNA, Messenger/analysis , Receptors, Interleukin-9/analysis , Receptors, Interleukin-9/geneticsABSTRACT
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-1ß. 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.
Subject(s)
Caveolin 1/metabolism , Down-Regulation , Nasal Polyps/metabolism , Rhinitis/metabolism , Sinusitis/metabolism , Adolescent , Adult , Aged , Case-Control Studies , Caveolin 1/genetics , Cyclin D1/genetics , Cyclin D1/metabolism , Female , Humans , Immunohistochemistry , Interferon-gamma/pharmacology , Interleukin-1beta/pharmacology , Interleukin-4/pharmacology , Male , Middle Aged , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , RNA, Messenger , Real-Time Polymerase Chain Reaction , Young AdultABSTRACT
BACKGROUND: The pathogenesis of human chronic rhinosinusitis with nasal polyps (CRSwNP) comprising eosinophilic CRSwNP (ECRSwNP) and non-eosinophilic (nECRSwNP) is not completely understood. Recent evidence has suggested that platelet-derived growth factor receptor alpha (PDGFRα) is implicated in cell growth, transformation, proliferation, migration, and vascular permeability and platelet-derived growth factor-A (PDGF-A) is a specific ligand for PDGFRα. However, little is known about their roles in CRSwNP. Therefore, we aimed to investigate the expression and role of PDGFRα and PDGF-A in CRSwNP. METHODS: PDGFRα protein expression was investigated by immunohistochemistry method and messenger RNA (mRNA) expression of PDGFRα and PDGF-A were assessed by real-time polymerase chain reaction (PCR) in CRSwNP patients and control subjects. Moreover, the effects of various stimulators with different concentrations and time on PDGFRα were evaluated on nasal explant culture. RESULTS: Quantitative analysis of immunostaining for PDGFRα showed an obvious elevation in immunolabeling of PDGFRα in CRSwNP groups compared with controls. Furthermore, PDGFRα protein was significantly stronger expressed in ECRSwNP group than nECRSwNP group and atopic patients showed stronger expression of PDGFRα protein than nonatopic patients. The mRNA of PDGFRα and PDGF-A were overexpressed in CRSwNP, especially in ECRSwNP. PDGFRα mRNA expression was closely related to PDGF-A mRNA. In nasal explant culture and stimulation, PDGFRα mRNA was augmented by interleukin 4 (IL-4), IL-5, or IL-1ß respectively, but suppressed by IL-27. CONCLUSION: PDGFRα may play a pivotal role in the pathophysiology of ECRSwNP and nECRSwNP by combining with PDGF-A. IL-4, IL-5, or IL-1ß may be critical for PDGFRα gene expression.
