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ABSTRACT: Background: The interleukin-6 (IL-6) pathway is known to be important in Th17 cell differentiation and in the pathology of many inflammatory disorders. However, the significance of the IL-6 pathway in nasal polyposis (NP) in Chinese patients remains unclear. Objective: The aim of this study was to evaluate the functions of the IL-6 pathway in NP in Chinese patients. Methods: The levels of IL-6 pathway components, including IL-6, soluble IL-6 receptor (sIL-6R), phosphoSTAT3 (pSTAT3), and suppressor of cytokine signalling 3 (SOCS3), were assessed. The Th17 milieu was examined by measuring the levels of retinoid acid-related orphan receptor C (RORc) and IL-17A. Results: Levels of IL-6 pathway components, RORc, and IL-17A were significantly higher in both NP groups than in the control(p<0.05). Furthermore, significantly higher levels of pSTAT3, RORc, and IL-17A, and significantly lower levels of SOCS3 were found in the atopic group than in the non-atopic group(P<0.05). IL-6 and sIL-6R levels were not significantly different between the 2 NP groups(P>0.05). pSTAT3 exhibited significantly positive correlations with RORc and IL-17A(P<0.01). Conclusions: The expression levels of the IL-6 pathway components were significantly higher in NP patients. Moreover, p-STAT3 levels were much higher in the atopic group, and were associated with a more severe Th17 response. These results suggest that the IL-6 pathway may play a crucial role in the pathology of NP in Chinese patients, and atopy may contribute to NP by affecting the IL-6 pathway.
Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 03/2013; 31(1):11-9. · 0.65 Impact Factor
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ABSTRACT: BACKGROUND: A predominant Th17 population and impaired Treg function is the marker of nasal polyposis (NP) in Chinese patients. TGF-β1, a multifunction cytokine, is a vital factor involved in inducing or restricting specific Th cell development. However, its role in NP has still not been well understood. METHODS: In a double-blind trial, 30 subjects were randomized into 2 groups (15 steroid-treated NP, 15 untreated NP), and 15 normal subjects were allocated as control group. We analyzed the expression of TGF-β1, p-Smad2, p-STAT3, Smad7, SOCS3, IL-10, IL-17A, Foxp3, and RORc in the NP tissue of Chinese patients using mRNA and protein detection methods. RESULTS: TGF-β1, p-Smad2, IL-10, SOCS3, and Foxp3 expression was higher in steroid-treated NP patients than in untreated NP patients. Conversely, expression of p-STAT3, Smad7, IL-17A, and RORc was higher in untreated NP patients than in steroid-treated NP patients, demonstrating that TGF-β1 was more likely to contribute to Treg commitment in Chinese NP patients after intranasal steroid treatment. CONCLUSIONS: TGF-β1 may be a signature Treg cytokine, which is valuable for obtaining a clear understanding of the pathogenesis of NP. Moreover, intranasal steroid treatment attenuated the chronic inflammatory response in these patients by promoting Smad-dependent Treg functions and reducing STAT3-mediated Th17 reactions.
Agents and Actions 11/2012; · 1.59 Impact Factor
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ABSTRACT: PURPOSE: Nasal polyposis (NP) is a chronic inflammatory disease that is characterized by increased populations of Th17 cells and impairment of Treg cells function in Chinese patients. Recent studies have shown that signal transducer and activator of transcription 3 (STAT3) and STAT5 are indispensable in the development and maintenance of Th17 and Treg cells. We investigated the roles of STAT3 and STAT5 in the imbalance of Th17 and Treg cells in NP. MATERIALS AND METHODS: The levels of IL-6, IL-2, pSTAT3, pSTAT5, SOCS3, RORc, Foxp3, IL-17A, and TGF-β1 were measured in patients with atopic NP, patients with nonatopic NP, and controls. We also evaluated the local distribution of Th17 and Treg cells by double immunofluorescence staining and the correlations between activated STAT3/STAT5 and Th17/Treg cell development were assessed. RESULTS: Increased levels of IL-6, pSTAT3, SCOS3, RORc, IL-17A, and CD4(+) RORc(+) cells, and decreased levels of IL-2, pSTAT5, Foxp3, TGF-β1, and CD4(+) Foxp3(+) cells were detected in both NP groups compared to controls (P < .05). The differences in all expression levels (except for IL-6) were significant between atopic and nonatopic patients (P < .05). There was a positive correlation between pSTAT3/pSTAT5 levels and Th17/Treg development and a negative correlation between SOCS3 and pSTAT3 in NP (P < 0.01). CONCLUSIONS: The results suggest that STAT3 and STAT5 may function through the IL-6 and IL-2 pathways to play a role in the imbalance of Th17/Treg in NP. An even more exaggerated imbalance of Th17/Treg caused by atopy may be correlated to the improper ratio of activated STAT3/STAT5.
American journal of otolaryngology 09/2012; · 0.77 Impact Factor
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ABSTRACT: Transforming growth factor-β1 (TGF-β1) plays a key role in the tissue remodeling processes involved in chronic rhinosinusitis (CRS), with the biological functions of secreted TGF-β1 regulated by multiple proteins. Among these regulators, latency-associated peptide and latent TGF-β-binding protein inhibit TGF-β1 function, whereas different proteases and integrins activate it. Progress in understanding the factors responsible for the bioactivity and expression of TGF-β1 has revealed that the dysregulation of TGF-β1 activation and expression is closely associated with the chronic respiratory inflammatory diseases involved in CRS. This review of the regulation of TGF-β1 activation and expression provides insight into the mechanism responsible for the different CRS subtypes, which will help further the investigation of novel therapy targets for the treatment of CRS.
ORL 06/2012; 74(3):172-8. · 0.91 Impact Factor
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ABSTRACT: Nasal polyposis (NP) is a chronic inflammatory disease of the nasal cavity and sinuses. Th17 cells have been considered to play roles in allergic airway diseases and various chronic inflammatory disorders.
This study aimed to investigate the population and function of peripheral Th17 cells in response to house dust mite extracts (HDM) allergen in NP patients, and evaluate the possible correlation between Th17 cells and atopy, to explore the role of atopy in the pathogenesis of NP.
Peripheral blood mononuclear cells (PBMCs) obtained from atopic NP patients, non-atopic NP patients, and controls were stimulated by phytohemagglutinin (PHA) or HDM plus PHA. The resulting frequency of Th17 cells was detected by flow cytometry and the expression of RORc was measured by real-time PCR. Then the concentrations of IL-17A, INF-γ, IL-4 and IL-5 in the supernatants were assayed by specific ELISAs.
The population and function of Th17 cells in allergen stimulated PBMCs were significantly higher in atopic NP patients. In addition, in atopic group, HDM+PHA stimulation induced significant increase of Th17 population and IL-17A production versus those in PHA stimulated ones. However, the frequency of Th17 cells was not correlated with Th1, Th2 cytokine productions.
Th17 immunity is involved in the systemic immune responses to allergen in atopic NP and atopy may aggravate NP by stimulating the increase of Th17 population and IL-17A production. The mechanism of Th17 cells response to allergen may be regulated differently from the regulation of Th1 and Th2 immunity in NP.
International immunopharmacology 12/2011; 12(1):235-40. · 2.21 Impact Factor
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ABSTRACT: To observe the distribution of Th17 cells and Foxp3(+);CD4(+);CD25(+); regulatory T cells in peripheral blood of patients with nasal polyposis(NP) and their correlation with clinical patients' condition, and to explore the role of Th17/Treg cell ratio imbalance in pathogenesis of nasal polyposis and significance.
The frequencies of Th17 cells and Treg cells were determined in 46 patients with NP and 10 controls by flow cytometry. The 46 patients were divided into two groups according to endoscopy score and CT score: the 1 group (endoscopy score: 2-8 scores; CT score: 3-10 scores, n=23) and the 2 group (endoscopy score: 8-12 scores; CT score: 10-19 scores, n=23).
Th17 cells were significantly higher in the blood of patients with NP compared with the control group (P<0.01), and the percentage was higher in the 2 group than the 1 group (P<0.05). The frequency of Treg cells was significantly decreased in patients with NP compared to the control group (P<0.01), whereas the difference between two groups was not significant. The ratio of Th17/Treg cells was highest in the 2 group (P<0.01), lower in the 1 group (P<0.01) and lowest in control subjects, and the differences were also significant between two groups (P<0.05). Furthermore, it was confirmed that the ratio of Th17/Treg positively correlated with endoscopy score and CT score (P<0.01).
The imbalance of Th17/Treg cell ratio characterized by increased Th17 cells and decreased Treg cells exists in peripheral blood of NP patients and may play an important role in the onset and development of NP. The degree of Th17/Treg cell imbalance may associate with clinical presentation.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 12/2011; 27(12):1339-42.
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ABSTRACT: To observe the distribution of Thl7 cells and Foxp3 CD4 * CD25 regulatory T cells in peripheral blood of patients with nasal polyposis(NP) and their correlation with clinical patients' condition, and to explore the role of Thl7/Treg cell ratio imbalance in pathogenesis of nasal polyposis and significance.
The frequencies of Thl7 cells and Treg cells were determined in 46 patients with NP and 10 controls by flow cytometry. The 46 patients were divided into two groups according to endoscopy score and CT score: the 1 group (endoscopy score: 2-8 scores; CT score: 3 -10 scores, n = 23) and the 2 group (endoscopy score: 8 -12 scores; CT score: 10 -19 scores, n = 23).
Thl7 cells were significantly higher in the blood of patients with NP compared with the control group (P<0.01), and the percentage was higher in the 2 group than the 1 group (P<0.05). The frequency of Treg cells was significantly decreased in patients with NP compared to the control group (P < 0. 01), whereas the difference between two groups was not significant. The ratio of Thl7/Treg cells was highest in the 2 group (P < 0.01), lower in the 1 group (P<0.01) and lowest in control subjects, and the differences were also significant between two groups (P<0.05). Furthermore, it was confirmed that the ratio of Thl7/Treg positively correlated with endoscopy score and CT score (P <. 0.01).
The imbalance of Thl7/Treg cell ratio characterized by increased Thl7 cells and decreased Treg cells exists in peripheral blood of NP patients and may play an important role in the onset and development of NP. The degree of Thl7/Treg cell imbalance may associate with clinical presentation.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 12/2011; 27(12):1339-42.
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ABSTRACT: Interleukin-17A (IL-17A) is a key inflammatory cytokine in many disorders, while the significance of IL-17A in nasal polyposis (NP) is still obscure. This study aimed to investigate the expression of IL-17A in nasal polyps from both atopic and nonatopic patients and its associations with clinical and histological features.
In all, 30 patients with NP were included, and were grouped into atopic and nonatopic patients according to skin prick test (SPT). Disease severity was evaluated by symptom score, endoscopy score and CT score. Histological characteristics were assessed by eosinophilic infiltration, basement membrane (BM) thickness, epithelial damage, squamous metaplasia, and goblet cell hyperplasia. IL-17A expression in polyps was detected by ELISA and immunohistochemistry.
Endoscopy score and CT score were significantly higher in atopic NP patients than in nonatopic NP patients (p < 0.05). IL-17A levels were significantly upregulated in both atopic (p < 0.01) and nonatopic (p < 0.05) patients versus controls. Furthermore, IL-17A levels were significantly higher in the atopic group versus nonatopic group. Significantly positive correlations were found between IL-17A levels and CT scores, eosinophilic infiltration and BM thicknesses.
These results indicated that expression of IL-17A was significantly upregulated in NP patients and was more severe in atopic NP patients, suggesting that IL-17A may play an important role in the pathology of NP and atopy may contribute to NP by stimulating the production of IL-17A.
Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 06/2011; 29(2):169-75. · 0.65 Impact Factor
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ABSTRACT: Nasal polyposis (NP) is a chronic inflammatory disease of the nasal cavity and sinuses that is regulated by T lymphocyte subsets. Imbalance of Th17/Treg has been considered critical in the development of inflammation and atopic reactions. To assess whether the balance of Th17/Treg is disrupted in patients with NP, we evaluated the distribution of Th17 and Treg cells among peripheral blood mononuclear cells (PBMCs) in atopic patients with NP, non-atopic patients with NP and controls. We then determined mRNA levels of RORc and Foxp3 and protein levels of IL-17, TGF-β and IL-10 in polyp tissue among the three groups. Finally, we investigated the correlation between Th17-, Treg- and Th1-, Th2-related cytokines (INF-γ, IL-4, IL-5). The results demonstrated that both atopic and non-atopic patients with NP revealed significantly increased Th17 proportion and decreased Treg proportion in PBMCs, as well as significantly increased RORc and IL-17 levels and decreased Foxp3 and TGF-β levels in polyp tissue. Furthermore, these differences were significant between atopic and non-atopic groups. The frequency of Treg in PBMCs was found to be negatively correlated with Th1 and Th2 cytokines in polyps. These results indicated that an impaired balance of Th17/Treg existed in patients with NP and was more severe in atopic patients, suggesting that the imbalance of Treg/Th17 may play an important role in the development of NP and that atopy may aggravate NP by promoting the imbalance of Th17/Treg.
Scandinavian Journal of Immunology 03/2011; 74(2):176-85. · 2.23 Impact Factor
