Hai Wang1, Zhi-Yong Li2, Wen-Xiu Jiang1, Bo Liao1, Guan-Ting Zhai1, Nan Wang1, Zhen Zhen3, Jian-Wen Ruan1, Xiao-Bo Long1, Heng Wang1, Wei-Hong Liu4, Geng-Tian Liang5, Wei-Min Xu6, Atsushi Kato7, Zheng Liu1. 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.
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.
Authors: Michael Elias; Shuai Zhao; Hongnga T Le; Jie Wang; Markus F Neurath; Clemens Neufert; Claudio Fiocchi; Florian Rieder Journal: J Clin Invest Date: 2021-01-19 Impact factor: 14.808
Authors: Atsushi Kato; Anju T Peters; Whitney W Stevens; Robert P Schleimer; Bruce K Tan; Robert C Kern Journal: Allergy Date: 2021-09-15 Impact factor: 14.710
Authors: Dong Kyu Kim; Seong Il Kang; Il Gyu Kong; Young Hoon Cho; Seul Ki Song; Se Jin Hyun; Sung Dong Cho; Sang Yoon Han; Seong Ho Cho; Dae Woo Kim Journal: Allergy Asthma Immunol Res Date: 2018-09 Impact factor: 5.764