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J Allergy Clin Immunol. 2018 May;141(5):1646-1658. doi: 10.1016/j.jaci.2017.12.972. Epub 2017 Dec 21.

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

Author information

1
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhengliuent@hotmail.com.
3
Department of Otolaryngology-Head and Neck Surgery, Peking University First Hospital, Beijing, China.
4
Department of Otolaryngology-Head and Neck Surgery, Wuhan No. 1 Hospital, Wuhan, China.
5
Department of Otolaryngology-Head and Neck Surgery, Wuhan No. 3 Hospital, Wuhan, China.
6
Department of Otolaryngology-Head and Neck Surgery, Wuhan Pu'ai Hospital, Wuhan, China.
7
Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.

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.

KEYWORDS:

Activate; IL-17; IL-36; chronic rhinosinusitis; elastase; nasal polyps; neutrophil

PMID:
29274415
DOI:
10.1016/j.jaci.2017.12.972

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