51. The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis.
- Author
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Wang H, Li ZY, Jiang WX, Liao B, Zhai GT, Wang N, Zhen Z, Ruan JW, Long XB, Wang H, Liu WH, Liang GT, Xu WM, Kato A, and Liu Z
- Subjects
- Cells, Cultured, Chronic Disease, Cytokines metabolism, Epithelial Cells metabolism, Epithelial Cells pathology, Gene Expression physiology, Humans, Inflammation pathology, Interleukin-1beta metabolism, Matrix Metalloproteinase 9 metabolism, Nasal Mucosa metabolism, Nasal Mucosa pathology, Nasal Polyps metabolism, Nasal Polyps pathology, Neutrophils pathology, Receptors, Interleukin-1 metabolism, Rhinitis pathology, Sinusitis pathology, Up-Regulation physiology, Inflammation metabolism, Interleukin-1 metabolism, Neutrophils metabolism, Rhinitis metabolism, Sinusitis metabolism
- Abstract
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: This study sought 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-36γ was detected by Western blotting. Dispersed nasal polyp cells were treated with IL-36γ with or without elastase inhibitor and dexamethasone., Results: Neutrophil infiltration and expression of IL-36 cytokines and IL-36R were upregulated 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 upregulated 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 matrix metalloproteinase 9; IL-17A; and chemokine (C-X-C motif) ligands 1, 2, and 8 from dispersed nasal polyp cells, which was abolished by elastase inhibitor. The proinflammatory effect of IL-36γ was not suppressed by dexamethasone., Conclusions: Increased production and activation of IL-36γ may act on neutrophils and further exaggerate neutrophilic inflammation in CRS., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
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