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The Activation And Function Of IL-36γ In Neutrophilic Inflammation In Chronic Rhinosinusitis

Posted on:2019-03-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z Y LiFull Text:PDF
GTID:1364330548455282Subject:Department of Otolaryngology Head and Neck Surgery
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Background:Although increased accumulation of neutrophils has been noted in chronic rhinosinusitis(CRS),the function and regulation of neutrophils in CRS are largely unknown.IL-36 family cytokines may play an important role in neutrophilic inflammation.Objective:To investigate the expression and function of IL-36 cytokines in CRS.Methods:Quantitative RT-PCR,immunohistochemistry,immunofluorescence,and ELISA were used to investigate the expression of IL-36 cytokines and IL-36 receptor(IL-36R)in sinonasal mucosa.The expression of IL-36R on neutrophils in polyps and blood was measured by flow cytometry.Purified blood neutrophils were cultured to investigate the regulation of IL-36R expression.The cleavage of IL-36y was detected by Western blotting.Dispersed nasal polyp cells(DNPCs)were treated with IL-36y with or without elastase inhibitor and dexamethasone.Results:Neutrophil infiltration and expression of IL-36 cytokines and IL-36R were up-regulated in both CRS with and without nasal polyps.IL-36y was the most abundant isoform and mainly expressed by epithelial cells in CRS.Neutrophils were the principal IL-36R+ cell type in polyps.IL-36R expression was almost absent in blood neutrophils and up-regulated by IL-6,IL-1β,and Dermatophagoides pteronyssinus group 1.Elastase activity was increased in polyps and degraded full-length IL-36y.Consistently,the levels of cleaved IL-36γ were increased in polyps.Full-length IL-36y promoted the production of MMP-9,IL-17A,CXCL1,CXCL2 and CXCL8 from DNPCs,which was abolished by elastase inhibitor.The pro-inflammatory effect of IL-36y was not suppressed by dexamethasone.Conclusion:Increased production and activation of IL-36y may act on neutrophils and further exaggerate neutrophilic inflammation in CRS.
Keywords/Search Tags:activate, elastase, interleukin 17, interleukin 36, neutrophil, chronic rhinosinusitis, nasal polyps
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