The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis
| Autor: | Zhi-Yong Li, Wen Xiu Jiang, Zhen Zhen, Bo Liao, Geng Tian Liang, Zheng Liu, Guan Ting Zhai, Heng Wang, Wei-Min Xu, Wei-Hong Liu, Atsushi Kato, Nan Wang, Jian wen Ruan, Hai Wang, Xiao Bo Long |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chemokine Neutrophils Interleukin-1beta Immunology Gene Expression Proinflammatory cytokine 03 medical and health sciences Nasal Polyps 0302 clinical medicine otorhinolaryngologic diseases medicine Humans Immunology and Allergy Nasal polyps Protease-activated receptor Sinusitis Cells Cultured Rhinitis Inflammation biology business.industry Elastase Receptors Interleukin-1 Epithelial Cells medicine.disease Up-Regulation Nasal Mucosa Elastase inhibitor 030104 developmental biology Matrix Metalloproteinase 9 Myeloperoxidase Chronic Disease biology.protein Cytokines Interleukin 17 business Interleukin-1 030215 immunology |
| Zdroj: | Journal of Allergy and Clinical Immunology. 141:1646-1658 |
| ISSN: | 0091-6749 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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