Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approach...Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.展开更多
Nasal polyp(NP) is a common chronic inflammatory disease of the nasal cavity and sinuses. Although some authors have suggested that NP is related to inflammatory factors such as interleukin(IL)-1β, IL-5, IL-8, granul...Nasal polyp(NP) is a common chronic inflammatory disease of the nasal cavity and sinuses. Although some authors have suggested that NP is related to inflammatory factors such as interleukin(IL)-1β, IL-5, IL-8, granulocyte-macrophage colony-stimulating factor(GM-CSF), tumor necrosis factor(TNF)-α, and IL-17, the mechanisms underlying the pathogenesis and progression of NP remain obscure. This study investigated the expression and distribution of IL-17 and syndecan-1 in NP, and explored the roles of these two molecules in the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps(Eos CRSwNP) and non-Eos CRSwNP. Real-time PCR and immunohistochemistry were used to detect the expression of IL-17 and syndecan-1 in samples [NP, unciform process(UP) from patients with CRS, and middle turbinate(MT) from healthy controls undergoing pituitary tumor surgery]. The results showed that the expression levels of IL-17 and syndecan-1 were upregulated in both NP and UP tissues, but both factors were higher in NP tissues than in UP tissues. There was no significant difference in IL-17 levels between the Eos CRSw NP and non-Eos CRSwNP samples, and syndecan-1 levels were increased in the non-Eos CRSwNP tissues as compared with those in Eos CRSwNP tissues. In all of the groups, there was a close correlation between the expression of IL-17 and syndecan-1 in nasal mucosa epithelial cells, glandular epithelial cells, and inflammatory cells, suggesting that IL-17 and syndecan-1 may play a role, and interact with each other, in the pathogenesis of non-Eos CRSwNP.展开更多
Recent studies indicated that interleukin（IL）-17, growth-related oncogene（GRO）-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the ...Recent studies indicated that interleukin（IL）-17, growth-related oncogene（GRO）-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction（RT-PCR） was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.展开更多
The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor（IL-17R） in intestinal mucosa tissue in patients with ulcerative colitis（UC） and con-trols, and evaluate their r...The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor（IL-17R） in intestinal mucosa tissue in patients with ulcerative colitis（UC） and con-trols, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein（CRP） levels were determined by ELISA and immu-nonephelometry, respectively. The IL-17 R m RNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls（P〈0.05）. Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase（P〈0.05）, and correlated with CRP levels（r=0.578, P〈0.01）. IL-17 R expression levels were higher in active UC patients than in healthy con-trols（P〈0.05）. It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.展开更多
OBJECTIVES: To study the concentration, distribution and expression of IL-5 in nasal polyp tissues and explore its significance in micro-environment differentiation of eosinophil accumulation. METHODS: The concentrati...OBJECTIVES: To study the concentration, distribution and expression of IL-5 in nasal polyp tissues and explore its significance in micro-environment differentiation of eosinophil accumulation. METHODS: The concentration and expression of IL-5 in nasal polyp tissues of 40 patients were determined by ELISA and immunohistochemistry and inferior turbinate mucosa from patients with nasal polyps and healthy volunteers were used as control. RESULTS: IL-5 concentration in polyp tissues was significantly higher than that in turbinate mucosa (P 0.05). IL-5 concentrations in polyp tissues were markedly higher in patients with allergic rhinitis compared with those without (P 0.05). 80.1% of the eosinophils were positive for IL-5 and 90.9% of IL-5 positive cells were eosinophils. Only 3.7% of lymphocytes and neutrophils were positive for IL-5; IL-5 was not detectable in epithelial cells. IL-5 expression in eosinophils of polyp tissues was remarkably stronger than that of the turbinate mucosa (P 0.05). IL-5 expression of eosinophils in polyp tissue was significantly stronger in patients with allergic rhinitis compared with those without (P 0.05). CONCLUSION: IL-5 is the key cytokine in eosinophilic pathologic mechanisms in nasal polyp tissues.展开更多
基金supported by the National Natural Science Foundation of China(NO.81570675,NO.31872742)Clinical Innovation Foundation of Southwest Hospital(SWH2017JCZD-06)Top Talent Training Programme Foundation of Southwest Hospital(SWH2018BJKJ-04).
文摘Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.
基金supported by grants from Research and National Promotion of Early Detection,Standardized Diagnosis and Treatment,and Preventive Strategy for Major Otology and Rhinologic Diseases(No.201202005)Wu Jieping Medical Foundation(No.LC1345)+1 种基金Foundation of Hubei Province Key Laboratory of Molecular Imaging(No.02.03.2013-64)the Natural Science Foundation of Hubei Province,China(No.2014CFB359)
文摘Nasal polyp(NP) is a common chronic inflammatory disease of the nasal cavity and sinuses. Although some authors have suggested that NP is related to inflammatory factors such as interleukin(IL)-1β, IL-5, IL-8, granulocyte-macrophage colony-stimulating factor(GM-CSF), tumor necrosis factor(TNF)-α, and IL-17, the mechanisms underlying the pathogenesis and progression of NP remain obscure. This study investigated the expression and distribution of IL-17 and syndecan-1 in NP, and explored the roles of these two molecules in the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps(Eos CRSwNP) and non-Eos CRSwNP. Real-time PCR and immunohistochemistry were used to detect the expression of IL-17 and syndecan-1 in samples [NP, unciform process(UP) from patients with CRS, and middle turbinate(MT) from healthy controls undergoing pituitary tumor surgery]. The results showed that the expression levels of IL-17 and syndecan-1 were upregulated in both NP and UP tissues, but both factors were higher in NP tissues than in UP tissues. There was no significant difference in IL-17 levels between the Eos CRSw NP and non-Eos CRSwNP samples, and syndecan-1 levels were increased in the non-Eos CRSwNP tissues as compared with those in Eos CRSwNP tissues. In all of the groups, there was a close correlation between the expression of IL-17 and syndecan-1 in nasal mucosa epithelial cells, glandular epithelial cells, and inflammatory cells, suggesting that IL-17 and syndecan-1 may play a role, and interact with each other, in the pathogenesis of non-Eos CRSwNP.
基金supported by grants from Research and National Promotion of Early Detection,Standardized Diagnosisand Treatment,and Preventive Strategy for Major Otology and Rhinologic Diseases(No.201202005)Wu Jieping Medical Foundation(No.LC1345)Foundation of Hubei ProvinceKey Laboratory of Molecular Imaging(No.02.03.2013-64)
文摘Recent studies indicated that interleukin（IL）-17, growth-related oncogene（GRO）-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction（RT-PCR） was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.
基金supported by the National Natural Science Foundation of China(No.81200283)
文摘The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor（IL-17R） in intestinal mucosa tissue in patients with ulcerative colitis（UC） and con-trols, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein（CRP） levels were determined by ELISA and immu-nonephelometry, respectively. The IL-17 R m RNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls（P〈0.05）. Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase（P〈0.05）, and correlated with CRP levels（r=0.578, P〈0.01）. IL-17 R expression levels were higher in active UC patients than in healthy con-trols（P〈0.05）. It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.
基金ThisworkwassupportedbytheNationalOutstandingYouthFoundationofChina (No.39725025)andtheNaturalScienceFoundationofGuangdongProvince (No .K 160 )
文摘OBJECTIVES: To study the concentration, distribution and expression of IL-5 in nasal polyp tissues and explore its significance in micro-environment differentiation of eosinophil accumulation. METHODS: The concentration and expression of IL-5 in nasal polyp tissues of 40 patients were determined by ELISA and immunohistochemistry and inferior turbinate mucosa from patients with nasal polyps and healthy volunteers were used as control. RESULTS: IL-5 concentration in polyp tissues was significantly higher than that in turbinate mucosa (P 0.05). IL-5 concentrations in polyp tissues were markedly higher in patients with allergic rhinitis compared with those without (P 0.05). 80.1% of the eosinophils were positive for IL-5 and 90.9% of IL-5 positive cells were eosinophils. Only 3.7% of lymphocytes and neutrophils were positive for IL-5; IL-5 was not detectable in epithelial cells. IL-5 expression in eosinophils of polyp tissues was remarkably stronger than that of the turbinate mucosa (P 0.05). IL-5 expression of eosinophils in polyp tissue was significantly stronger in patients with allergic rhinitis compared with those without (P 0.05). CONCLUSION: IL-5 is the key cytokine in eosinophilic pathologic mechanisms in nasal polyp tissues.
