Chen Meng-Bing, Li Meng-Hua, Wu Li-Yuan, Wang Rong, Long Xi, Zhang Liang, Sun Wei, Guo Wei-Wei, Pan Yong, Zhang Yun-Shi, Lin Chang, Shi Xi, Yang Shi-Ming
The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, China; College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853, China; Ankang People's Hospital, Ankang 725000, Shanxi, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, Hainan, China; Academician Workstation of Hainan University (School of Pharmaceutical Sciences), Yazhou Bay, Sanya 572000, Hainan, China; Artificial Auditory Laboratory of Jiangsu Province, Xuzhou Medical University, Xuzhou 221000, Jiangsu, China.
Biochem Pharmacol. 2023 Apr;210:115457. doi: 10.1016/j.bcp.2023.115457. Epub 2023 Feb 16.
NOD-like receptor protein 3 (NLRP3) inflammasomes trigger the inflammatory cascades and participate in various inflammatory diseases, including noise-induced hearing loss (NIHL) caused by oxidative stress. Recently, the anti-inflammatory traditional medicine oridonin (Ori) has been reported to provide hearing protection in mice after noise exposure by blocking the NLRP3-never in mitosis gene A-related kinase 7 (NEK7)-inflammasome complex assembly. Using RNA sequencing analysis, we further elucidated that interleukin 1 receptor type 2 (IL1R2) may be another crucial factor regulated by Ori to protect NIHL. We observed that IL1R2 expression was localized in spiral ganglion neurons, inner and outer hair cells, in Ori-treated mouse cochleae. Additionally, we confirmed that ectopic overexpression of IL1R2 in the inner ears of healthy mice using an adeno-associated virus delivery system significantly reduced noise-induced ribbon synapse lesions and hearing loss by blocking the "cytokine storm" in the inner ear. This study provides a novel theoretical foundation for guiding the clinical treatment of NIHL.
NOD样受体蛋白3（NLRP3）炎性小体触发炎症级联反应，并参与各种炎症性疾病，包括由氧化应激引起的噪声性听力损失（NIHL）。最近，有报道称，抗炎传统药物冬凌草甲素（Ori）通过阻断NLRP3-有丝分裂期基因A相关激酶7（NEK7）-炎性小体复合物组装，在噪声暴露后的小鼠中提供听力保护。通过RNA测序分析，我们进一步阐明白细胞介素1受体2型（IL1R2）可能是Ori调控以保护NIHL的另一个关键因素。我们观察到，在Ori处理的小鼠耳蜗中，IL1R2表达定位于螺旋神经节神经元、内毛细胞和外毛细胞。此外，我们证实，使用腺相关病毒递送系统在健康小鼠内耳中异位过表达IL1R2，通过阻断内耳中的“细胞因子风暴”，显著减少了噪声诱导的带状突触损伤和听力损失。本研究为指导NIHL的临床治疗提供了新的理论基础。
