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.
Original language | English (US) |
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Pages (from-to) | 1646-1658 |
Number of pages | 13 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 141 |
Issue number | 5 |
DOIs | |
State | Published - May 2018 |
Keywords
- Activate
- IL-17
- IL-36
- chronic rhinosinusitis
- elastase
- nasal polyps
- neutrophil
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology