Oridonin employs interleukin 1 receptor type 2 to treat noise-induced hearing loss by blocking inner ear inflammation
Brief intro:
- Author: Meng-Bing Chen, Meng-Hua Li, Li-Yuan Wu, Rong Wang, Xi Long, Liang Zhang, Wei Sun, Wei-Wei Guo, Yong Pan, Yun-Shi Zhang, Chang Lin, Xi Shi, Shi-Ming Yang
- Journal: Biochemical Pharmacology
- Doi: https://www.doi.org/10.1016/j.bcp.2023.115457
- Publication Date: 2023 Apr
Products/Services used in the paper
Quotation shows PackGene:The target gene overexpression adeno-associated virus (AAV) vector AAV8 [ssAAV.CMV.EGFP-P2A-mIL1R2.WPRE.SV40pA] (PackGene, Guangzhou, China) (IL1R2-AAV) was constructed and transduced into the inner ear through the semicircular canal to achieve gene transduction in cochlear auditory cells (with GFP-AAV as control).
Research Field:hearing
AAV Serotype:AAV8
Targeted organ:inner ear
Animal or cell line strain:Male C57BL/6J mice, aged 5–6 weeks
Abstract
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.
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