The activation and function of IL-36? in neutrophilic inflammation in chronic rhinosinusitis - 31/01/18
, Wen-Xiu Jiang, MD a, Bo Liao, MD, PhD a, Guan-Ting Zhai, MD a, Nan Wang, MD, PhD a, Zhen Zhen, MD, PhD b, Jian-wen Ruan, MD a, Xiao-Bo Long, MD, PhD a, Heng Wang, MD, PhD a, Wei-Hong Liu, MD, PhD c, Geng-Tian Liang, MD d, Wei-Min Xu, MD e, Atsushi Kato, PhD f, Zheng Liu, MD, PhD aCet article a été publié dans un numéro de la revue, cliquez ici pour y accéder
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.
Le texte complet de cet article est disponible en PDF.Key words : Activate, chronic rhinosinusitis, elastase, IL-17, IL-36, nasal polyps, neutrophil
Abbreviations used : CRS, CRSsNP, CRSwNP, Ct, CXCL, Der p1, DNPCs, ECP, HNECs, IL-36Ra, IL-1RAcP, MMP, MPO, PAR
Plan
| This study was supported by National Natural Science Foundation of China grants 81325006, 81570899, and 81630024 (Z.L.), 81200733 (H.W.), and 81400448 (X.B.L.), and Hubei Province Natural Science Foundation grant 2017CFA016 (Z.L.). |
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| Disclosure of potential conflict of interest: Z. Liu has received grants from National Natural Science Foundation of China and Hubei Province Natural Science Foundation. X.-B. Long has received a grant from National Natural Science Foundation of China. H. Wang has received a grant from National Natural Science Foundation of China. A. Kato has received a grant from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. |
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