Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
Biochem Biophys Res Commun. 2020 Jan 29;522(1):61-67. doi: 10.1016/j.bbrc.2019.11.031. Epub 2019 Nov 15.
Allergic rhinitis (AR) is a worldwide highly prevalent nasal inflammatory disease with elusive mechanisms about the regulation of innate immune response. The roles and mechanisms of NLRP3, a typical inflammasome, in AR development remain unclear. Here we investigate the roles of NLRP3 inflammasome activation in the development and progression of AR and try to uncover its potential mechanisms underlying. Wildtype and NLRP3 knockout mice were applied to construct the ovalbumin (OVA)-induced AR model. Caspase-1 specific inhibitor Belnacasan and inflammasome activator ATP were used for adjuvant stimulation of AR-model mice respectively. We found that the production of IL-1β and the activation of inflammasome were increased in both patients and mice with AR. NLRP3 deficiency markedly suppressed AR progression with reduced inflammatory response and epithelium pyroptosis in mice with AR. Furthermore, Caspase-1 inhibitor treatment in vivo ameliorated the development and progression of AR with favorable outcomes. Mechanistically, inflammation augments and nasal mucosa injury during AR were partially due to ASC-specks accumulation and subsequent cell pyroptosis. Our study reveals the previously unknown roles of NLRP3 inflammasome in promoting the development and progression of AR via enhancing inflammatory response and epithelium pyroptosis and thus provides a potential clue for allergic disease interventions.
变应性鼻炎（AR）是一种全球范围内高度流行的鼻内炎症性疾病，其先天免疫反应的调节机制尚不清楚。NLRP3 炎性小体作为一种典型的炎性小体，其在 AR 发展中的作用和机制仍不清楚。本研究旨在探讨 NLRP3 炎性小体激活在 AR 发展和进展中的作用，并试图揭示其潜在的机制。我们应用野生型和 NLRP3 敲除小鼠构建卵清蛋白（OVA）诱导的 AR 模型。分别使用 caspase-1 特异性抑制剂 Belnacasan 和炎性小体激活剂 ATP 对 AR 模型小鼠进行辅助刺激。结果发现，AR 患者和小鼠的 IL-1β 产生和炎性小体激活均增加。AR 小鼠中 NLRP3 缺失明显抑制了 AR 的进展，降低了炎症反应和上皮细胞焦亡。此外，体内 Caspase-1 抑制剂治疗改善了 AR 的发展和进展，效果良好。机制上，炎症加重和 AR 期间鼻黏膜损伤部分归因于 ASC 斑点的积累和随后的细胞焦亡。本研究揭示了 NLRP3 炎性小体通过增强炎症反应和上皮细胞焦亡促进 AR 发展和进展的未知作用，为过敏疾病的干预提供了潜在线索。
