| Nasal polyposis (NP) is an inflammatory diseases, which is featured bychronic inflammation of the nasal cavity and sinusitis mucosa, which has anestimated worldwide incidence rate of2%to4%, affecting quality of life andeconomical expenditures. The level of diagnosis and treatment of NP hasbeen greatly improved, however, the therapeutic effect of NP is still cannotmake patients satisfied completely, and the recurrence rate is also high. Inthe past decades, investigators had carried out extensive and in-depthresearch on aetiopathogenesis of NP. At present, several studies have provedthat the chronic inflammatory reaction of mucosa was featured by a largenumber of inflammatory cells infiltrations, causing by multiple factors suchas infection, inflammation, and anatomical variation. Moreover, apredominant Th17population and impaired Treg function is the marker ofNP in Chinese patients.TGF-β1, a multifunction cytokine, has many biological effects. It is avital factor involved in modulating immune responses and promoting tissue remodeling. Besides, TGF-β1is not only essential for Th17induction andIL-17secretion through the facilitation and prolongation of the STAT3pathway, but also is necessary for Treg cell generation via Smads pathway.Then, TGF-β1plays an important role in mucosal repairing process throughpromoting the secretion of ECM components and postponing themetabolism of ECM. However, it’s exactly role in NP has still not been wellunderstood.Our experiments attempt not only to test the expression levels ofTGF-β1and its downstream signaling proteins in NP tissues, but alsoanalyze the correlations between TGF-β1and Th17/Treg, in order to furtherdefine the role of TGF-β1in NP. Furthermore, we would study the effects ofintranasal steroids on TGF-β1and its downstream molecules expression,enriching the theoretical basis of INS on NP treatment.PART ONE Relativity analysis of TGF-β1and Th17/Treg in patientswith nasal polyposisObject: To explore the role of TGF-β1for Th17/Treg imbalance inChinese NP patients through testing the expression of TGF-β1, p-Smad2,Foxp3and RORc in NP tissues, and observing the distribution of Treg andTh17cells in peripheral bloods of Chinese sufferers with nasal polyps.Methods: A total of30participators were divided into two groups (15 NP patients,15controls). We analyzed the expression of TGF-β1, p-Smad2,Foxp3and RORc in the NP tissue of Chinese patients using mRNA andprotein detection methods. Besides, exerting the FCM method, we alsodetected the distribution of Treg and Th17cells in PBMCs. Finally, weexplored the correlation between TGF-β1and Treg/Th17cells.Results: TGF-β1, p-Smad2, Foxp3and Treg cells expression washigher in controls than in NP patients. Conversely, expression of Th17cellsand RORc was higher in NP patients than in controls, demonstrating thatTGF-β1was more likely to contribute to Treg commitment in Chinese NPpatients.Conclusions: TGF-β1may be a signature Treg cytokine via Smadsignaling pathway, which is valuable for inhibiting the inflammatoryresponse of NP. Moreover, the defect of Treg function in NP may cause bythe low level of TGF-β1.PART TWO Effect of intranasal steroids on Th17and Treg cells inpatients with nasal polyposisObject: In this section, INS acts as an intervention factor, and weobserve the effects of steroid administration on the expression of TGF-β1and the related molecules so as to further understand the pathogenesis of NPand broaden our knowledge about the mechanisms of steroid action. Methods: Thirty participators were designated into two groups (15untreated NP patients,15steroid-treated NP patients). We analyzed theexpression of TGF-β1, IL-10, IL-17A, SOCS3and Smad7by ELISA, anddetected the level of p-Smad2and p-STAT3proteins by WB and IHC. Theexpression of Foxp3and RORc in the NP tissues was investigated by mRNAdetection methods, and using the double immunofluorescence stainingmethod, we detected the CD4+RORc+and CD4+Foxp3+cells. Besides, thedistribution of Treg and Th17cells in PBMCs was observed via FCM.Finally, the BM thickness of NP was also measured by HE staining.Results: TGF-β1, p-Smad2, IL-10, SOCS3, Foxp3, and Tregexpression was higher in steroid-treated NP patients than in untreated NPpatients. Conversely, expression of p-STAT3, Smad7, IL-17A, RORc andTh17was higher in untreated NP patients than in steroid-treated NP patients,demonstrating that TGF-β1was more likely to contribute to Tregcommitment in Chinese NP patients.Conclusions: TGF-β1may be a negative regulator of the inflammatoryresponse in NP tissues. Moreover, intranasal steroid treatment attenuated thechronic inflammatory response in these patients by promotingSmad-dependent Treg functions and reducing STAT3-mediated Th17reactions. |
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