Eur Arch Otorhinolaryngol DOI 10.1007/s00405-014-3146-8
Rhinology
Downregulation of caveolin‑1 in chronic rhinosinusitis with and without nasal polyps Hai Lin · Dong Lin · Xi‑Sheng Xiong · Xiong‑Xiong Dai · Ting Lin
Received: 29 March 2014 / Accepted: 10 June 2014 © Springer-Verlag Berlin Heidelberg 2014
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 H. Lin Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, 83 Fenyang Road, Xuhui District, Shanghai 200031, China H. Lin Department of Otorhinolaryngology, Fuzhou General Hospital, Fuzhou 350025, Fujian, China D. Lin (*) · X.-X. Dai · T. Lin Department of Biology and Chemical Engineering, Fuqing Branch of Fujian Normal University, Fuqing 350300, Fujian, China e-mail: [email protected] X.-S. Xiong Department of Pathology, Fuzhou General Hospital, Fuzhou 350025, Fujian, China
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. Keywords Caveolin-1 · Caveolae · Cyclin D1 · Endothelial nitric oxide-synthase · Chronic rhinosinusitis · Nasal polyps
Introduction Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease, and its etiology and pathophysiology remain controversial [1, 2]. It has been showed that altered innate immunity, tissue remodeling, and effects of microorganisms may be involved in the pathogenesis of CRS [3]. However, the exact etiology of CRS needs to be further elucidated. Caveolin-1 (Cav-1) is a 22 kDa scaffolding protein in membrane invaginations termed caveolae. Morphologically, caveolae can be defined as 50- to 100-nm-diameter flask-shaped. Caveolae has been proven to be involved in the process of potocytosis, mediation of endocytosis and transcytosis of macromolecule as well as regulation of signal transduction pathway and caveolae plays a pivotal role in host defense against infections and tumour suppression by mediating the process of transcytosis, endocytosis, uptake of bacteria and viruses, intracellular trafficking and oncogenesis [4–6] and then reducing the production of cyclin D1 and endothelial nitric oxide-synthase (eNOS)
13
Eur Arch Otorhinolaryngol
Table 1 Characteristics of included studies Groups
No. of subjects Age (years) Gender (male/ female) Disease duration (years) Total VAS score Endoscopy score CT score Positive SPT, n (%)
Immunohistochemistry and real-time PCR
Nasal explant culture
CRSwNP
CRSsNP
Controls
27 17–71 16/11
23 16–69 13/10
15 15–67 8/7
12 15–63 6/6
3.6 ± 2.6*
2.1 ± 1.5
N/A
N/A
16.2 ± 3.9* 11.0 ± 3.3 N/A 9.0 ± 3.8* 6.3 ± 2.5 N/A 17.3 ± 3.0* 13.3 ± 3.8 N/A
N/A N/A N/A
11(40.7)
0
8(34.8)
0
PCR polymerase chain reaction; CRSwNP chronic rhinosinusitis with nasal polyps; CRSsNP chronic rhinosinusitis without nasal polyps; VAS visual analog scale; N/A not applicable; CT computed tomography; SPT skin-prick test * P
Rhinology
Downregulation of caveolin‑1 in chronic rhinosinusitis with and without nasal polyps Hai Lin · Dong Lin · Xi‑Sheng Xiong · Xiong‑Xiong Dai · Ting Lin
Received: 29 March 2014 / Accepted: 10 June 2014 © Springer-Verlag Berlin Heidelberg 2014
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 H. Lin Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, 83 Fenyang Road, Xuhui District, Shanghai 200031, China H. Lin Department of Otorhinolaryngology, Fuzhou General Hospital, Fuzhou 350025, Fujian, China D. Lin (*) · X.-X. Dai · T. Lin Department of Biology and Chemical Engineering, Fuqing Branch of Fujian Normal University, Fuqing 350300, Fujian, China e-mail: [email protected] X.-S. Xiong Department of Pathology, Fuzhou General Hospital, Fuzhou 350025, Fujian, China
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. Keywords Caveolin-1 · Caveolae · Cyclin D1 · Endothelial nitric oxide-synthase · Chronic rhinosinusitis · Nasal polyps
Introduction Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease, and its etiology and pathophysiology remain controversial [1, 2]. It has been showed that altered innate immunity, tissue remodeling, and effects of microorganisms may be involved in the pathogenesis of CRS [3]. However, the exact etiology of CRS needs to be further elucidated. Caveolin-1 (Cav-1) is a 22 kDa scaffolding protein in membrane invaginations termed caveolae. Morphologically, caveolae can be defined as 50- to 100-nm-diameter flask-shaped. Caveolae has been proven to be involved in the process of potocytosis, mediation of endocytosis and transcytosis of macromolecule as well as regulation of signal transduction pathway and caveolae plays a pivotal role in host defense against infections and tumour suppression by mediating the process of transcytosis, endocytosis, uptake of bacteria and viruses, intracellular trafficking and oncogenesis [4–6] and then reducing the production of cyclin D1 and endothelial nitric oxide-synthase (eNOS)
13
Eur Arch Otorhinolaryngol
Table 1 Characteristics of included studies Groups
No. of subjects Age (years) Gender (male/ female) Disease duration (years) Total VAS score Endoscopy score CT score Positive SPT, n (%)
Immunohistochemistry and real-time PCR
Nasal explant culture
CRSwNP
CRSsNP
Controls
27 17–71 16/11
23 16–69 13/10
15 15–67 8/7
12 15–63 6/6
3.6 ± 2.6*
2.1 ± 1.5
N/A
N/A
16.2 ± 3.9* 11.0 ± 3.3 N/A 9.0 ± 3.8* 6.3 ± 2.5 N/A 17.3 ± 3.0* 13.3 ± 3.8 N/A
N/A N/A N/A
11(40.7)
0
8(34.8)
0
PCR polymerase chain reaction; CRSwNP chronic rhinosinusitis with nasal polyps; CRSsNP chronic rhinosinusitis without nasal polyps; VAS visual analog scale; N/A not applicable; CT computed tomography; SPT skin-prick test * P
