PMID- 29274415 OWN - NLM STAT- MEDLINE DCOM- 20190729 LR - 20220606 IS - 1097-6825 (Electronic) IS - 0091-6749 (Linking) VI - 141 IP - 5 DP - 2018 May TI - The activation and function of IL-36gamma in neutrophilic inflammation in chronic rhinosinusitis. PG - 1646-1658 LID - S0091-6749(17)32924-X [pii] LID - 10.1016/j.jaci.2017.12.972 [doi] AB - 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-36gamma was detected by Western blotting. Dispersed nasal polyp cells were treated with IL-36gamma 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-36gamma 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-1beta, and Dermatophagoides pteronyssinus group 1. Elastase activity was increased in polyps and degraded full-length IL-36gamma. Consistently, the levels of cleaved IL-36gamma were increased in polyps. Full-length IL-36gamma 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-36gamma was not suppressed by dexamethasone. CONCLUSIONS: Increased production and activation of IL-36gamma may act on neutrophils and further exaggerate neutrophilic inflammation in CRS. CI - Copyright (c) 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. FAU - Wang, Hai AU - Wang H AD - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Li, Zhi-Yong AU - Li ZY AD - 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. FAU - Jiang, Wen-Xiu AU - Jiang WX AD - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liao, Bo AU - Liao B AD - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhai, Guan-Ting AU - Zhai GT AD - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Wang, Nan AU - Wang N AD - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhen, Zhen AU - Zhen Z AD - Department of Otolaryngology-Head and Neck Surgery, Peking University First Hospital, Beijing, China. FAU - Ruan, Jian-Wen AU - Ruan JW AD - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Long, Xiao-Bo AU - Long XB AD - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Wang, Heng AU - Wang H AD - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liu, Wei-Hong AU - Liu WH AD - Department of Otolaryngology-Head and Neck Surgery, Wuhan No. 1 Hospital, Wuhan, China. FAU - Liang, Geng-Tian AU - Liang GT AD - Department of Otolaryngology-Head and Neck Surgery, Wuhan No. 3 Hospital, Wuhan, China. FAU - Xu, Wei-Min AU - Xu WM AD - Department of Otolaryngology-Head and Neck Surgery, Wuhan Pu'ai Hospital, Wuhan, China. FAU - Kato, Atsushi AU - Kato A AD - Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. FAU - Liu, Zheng AU - Liu Z AD - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171221 PL - United States TA - J Allergy Clin Immunol JT - The Journal of allergy and clinical immunology JID - 1275002 RN - 0 (Cytokines) RN - 0 (IL36G protein, human) RN - 0 (Interleukin-1) RN - 0 (Interleukin-1beta) RN - 0 (Receptors, Interleukin-1) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) EIN - J Allergy Clin Immunol. 2022 Jun;149(6):2179. PMID: 35667751 MH - Cells, Cultured MH - Chronic Disease MH - Cytokines/metabolism MH - Epithelial Cells/metabolism/pathology MH - Gene Expression/physiology MH - Humans MH - Inflammation/*metabolism/pathology MH - Interleukin-1/*metabolism MH - Interleukin-1beta/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Nasal Mucosa/metabolism/pathology MH - Nasal Polyps/metabolism/pathology MH - Neutrophils/*metabolism/pathology MH - Receptors, Interleukin-1/metabolism MH - Rhinitis/*metabolism/pathology MH - Sinusitis/*metabolism/pathology MH - Up-Regulation/physiology OTO - NOTNLM OT - Activate OT - IL-17 OT - IL-36 OT - chronic rhinosinusitis OT - elastase OT - nasal polyps OT - neutrophil EDAT- 2017/12/24 06:00 MHDA- 2019/07/30 06:00 CRDT- 2017/12/24 06:00 PHST- 2017/06/25 00:00 [received] PHST- 2017/11/25 00:00 [revised] PHST- 2017/12/06 00:00 [accepted] PHST- 2017/12/24 06:00 [pubmed] PHST- 2019/07/30 06:00 [medline] PHST- 2017/12/24 06:00 [entrez] AID - S0091-6749(17)32924-X [pii] AID - 10.1016/j.jaci.2017.12.972 [doi] PST - ppublish SO - J Allergy Clin Immunol. 2018 May;141(5):1646-1658. doi: 10.1016/j.jaci.2017.12.972. Epub 2017 Dec 21.