Interleukin 8 exacerbates age-related hearing loss through regulating perivascular-resident macrophage-like melanocytes viability and the permeability of the endothelial cells.

Shuai Chen, Yi Zhou, Junhua Wu, Juli Lin, Zhicong Hong, Ye Wang, Yu Han, Xianyang Luo

Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361005, China; Xiamen Key Laboratory of Otolaryngology Head and Neck Surgery, Xiamen, Fujian 361005, China.Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361005, China; Xiamen Key Laboratory of Otolaryngology Head and Neck Surgery, Xiamen, Fujian 361005, China. · pubmed

Paper

Abstract

The etiology and mechanism causing Age-related hearing loss (ARHL) are not understood. This study aimed to investigate the molecular mechanism of interleukin 8 (IL-8) associated with ARHL. Sera content of IL-8 was significantly higher in patients with ARHL than normal volunteers and had a positive association with disease severity of ARHL. Human IL-8 (hIL-8) could exacerbate the progressive ARHL with time increase and promoted apoptosis of hair cells in cochlea. As the important component in maintaining the integrity of the blood-labyrinth barrier (BLB) and hearing function, cell viability of perivascular-resident macrophage-like melanocytes (PVM/Ms) was restrained while apoptosis of PVM/Ms was enhanced in the presence of hIL-8. Using a cell culture-based in vitro model, the permeability of the endothelial cells (ECs) monolayer increased markedly in the presence of IL-8-treated PVM/Ms or PVM/Ms-derived from LV5-hIL-8 mice as compared with the presence of PVM/Ms-derived from wild type (WT) mice or 12-months WT mice. Mechanistically, IL-8 exposure enhanced the expression of histone deacetylase 3 (HDAC3) in PVM/Ms and HDAC3 inhibitor significantly blocked the permeability of the ECs in the presence of IL-8-treated PVM/Ms. Besides, HDAC3 inhibitor had a protective effect on hIL-8-launched ARHL in mice. Collectively, the elevated of serum IL-8 in ARHL patients activated the activity of HDAC3 in PVM/Ms, subsequently increased the permeability of the ECs, resulting in the impairments of the BLB and hair cells in cochlea. Possibly, IL-8 could be used in the diagnosis of ARHL and these findings might help to identify the clinical therapeutic direction for ARHL.

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Research summary

The paper investigates the role of interleukin 8 in exacerbating age-related hearing loss, which is a condition associated with aging. While it explores a potential mechanism related to inflammation and cellular viability, it primarily focuses on the symptoms of age-related hearing loss rather than addressing the root causes of aging itself. The findings may contribute to understanding ARHL but do not significantly advance the broader field of longevity research or lifespan extension. Thus, it is rated as a solid but limited contribution.

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