PMID- 35809382 OWN - NLM STAT- MEDLINE DCOM- 20220817 LR - 20220817 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 110 DP - 2022 Sep TI - Activation of NLRP3 inflammasome contributes to the inflammatory response to allergic rhinitis via macrophage pyroptosis. PG - 109012 LID - S1567-5769(22)00496-9 [pii] LID - 10.1016/j.intimp.2022.109012 [doi] AB - OBJECTIVE: Allergic rhinitis (AR) is a heterogeneous disease and its pathogenesis is still unclear. Growing clinical evidence has thrown light on the key role of NOD-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation of allergic disease. However, the effect of NLRP3 activation in macrophages for AR has not been elucidated. This study aims to investigate the role of NLRP3 in ovalbumin (OVA)-stimulated bone marrow-derived macrophages (BMDMs) and to confirm the impact of macrophage pyroptosis in allergic rhinitis. METHODS: Nasal inflammation levels were assessed by H&E and dual immunofluorescence staining. BMDMs were cultured and were stimulated with OVA in the presence or absence of MCC950 to further investigate the effect of NLRP3 activation in macrophages. The cell lysates and supernatants were harvested to measure NLRP3 and downstream molecules, as well as cell rupture, and IL-1beta production. Besides, an OVA-exposed AR mouse model was developed, and the histopathology in nasal mucosa, and the relationship between macrophage pyroptosis and local inflammation were detected. The inhibitory role of MCC950 was also evaluated. RESULTS: The present results uncovered that the number of macrophages and NLRP3 expression were increased in the nasal mucosa of AR subjects, and upregulation of macrophage pyroptosis contributed to local allergic inflammation. In addition, the OVA challenge induced NLRP3 inflammasome activation in BMDMs, as evidenced by enhanced expressions of NLRP3-ASC-caspase-1 inflammasome, gasdermin D, production of IL-1beta, and increased macrophage lysis. Furthermore, inhibition of NLRP3 inflammasome attenuated nasal inflammation, accompanied by a reduced number of inflammatory cells and lower levels of IL-1beta and OVA-specific IgE. CONCLUSIONS: Our results indicate that NLRP3 inflammasome played an important role in allergic airway inflammation by activating macrophage's pyroptotic cell death and releasing inflammatory mediators to local tissues. Inhibition of NLRP3 inflammasome-mediated pyroptosis could be a promising therapeutic strategy for ameliorating inflammatory responses in allergic rhinitis. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Zhou, Huiqin AU - Zhou H AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Zhang, Wei AU - Zhang W AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Qin, Danxue AU - Qin D AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Liu, Peiqiang AU - Liu P AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Fan, Wenjun AU - Fan W AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Lv, Hao AU - Lv H AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Tan, Lu AU - Tan L AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Gao, Ziang AU - Gao Z AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: ziang.gao@whu.edu.cn. FAU - Xu, Yu AU - Xu Y AD - Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: xuy@whu.edu.cn. LA - eng PT - Journal Article DEP - 20220706 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Humans MH - *Inflammasomes/metabolism MH - Inflammation/metabolism MH - Interleukin-1beta/metabolism MH - Macrophages/metabolism MH - Mice MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Ovalbumin/metabolism MH - Pyroptosis MH - *Rhinitis, Allergic/metabolism OTO - NOTNLM OT - Allergic rhinitis OT - Inflammasome OT - MCC950 OT - Macrophage OT - NLRP3 OT - Pyroptosis EDAT- 2022/07/10 06:00 MHDA- 2022/08/18 06:00 CRDT- 2022/07/09 18:15 PHST- 2022/05/27 00:00 [received] PHST- 2022/06/23 00:00 [revised] PHST- 2022/06/27 00:00 [accepted] PHST- 2022/07/10 06:00 [pubmed] PHST- 2022/08/18 06:00 [medline] PHST- 2022/07/09 18:15 [entrez] AID - S1567-5769(22)00496-9 [pii] AID - 10.1016/j.intimp.2022.109012 [doi] PST - ppublish SO - Int Immunopharmacol. 2022 Sep;110:109012. doi: 10.1016/j.intimp.2022.109012. Epub 2022 Jul 6.