The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis

Publication date: Available online 21 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Hai Wang, Zhi-Yong Li, Wen-Xiu Jiang, Bo Liao, Guan-Ting Zhai, Nan Wang, Zhen Zhen, Jian-wen Ruan, Xiao-Bo Long, Heng Wang, Wei-Hong Liu, Geng-Tian Liang, Wei-Min Xu, Atsushi Kato, Zheng Liu
BackgroundAlthough 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.ObjectiveTo investigate the expression and function of IL-36 cytokines in CRS.MethodsQuantitative 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-36γ was detected by Western blotting. Dispersed nasal polyp cells (DNPCs) were treated with IL-36γ with or without elastase inhibitor and dexamethasone.ResultsNeutrophil infiltration and expression of IL-36 cytokines and IL-36R were up-regulated in both CRS with and without nasal polyps. IL-36γ 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-36γ. Consistently, the levels of cleaved IL-36γ were increased in polyps. Full-length IL-36γ 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-36γ was not suppressed by dexamethasone.ConclusionIncreased production and activation of IL-36γ may act on neutrophils and further exaggerate neutrophilic inflammation in CRS.



http://ift.tt/2BLMMPX