Low-Molecular-Weight Hyaluronic Acid Contributes to Noise-Induced Cochlear Inflammation

Guoping Zhang; Yiling Gao; Zhen Zhao; Ilmari Pyykko; Jing Zou

doi:10.1159/000530280

Low-Molecular-Weight Hyaluronic Acid Contributes to Noise-Induced Cochlear Inflammation

Audiol Neurootol. 2023;28(5):380-393. doi: 10.1159/000530280. Epub 2023 May 9.

Authors

Guoping Zhang¹, Yiling Gao^{1

2}, Zhen Zhao¹, Ilmari Pyykko³, Jing Zou^{1

4}

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Centre for Otolaryngology-Head and Neck Surgery of the Chinese PLA, Changhai Hospital, Second Military Medical University, Shanghai, China.
² Department of Otolaryngology-Head and Neck Surgery, Shidong Hospital, Shanghai, China.
³ Hearing and Balance Research Unit, Field of Otolaryngology, School of Medicine, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁴ Department for Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

PMID: 37231777
DOI: 10.1159/000530280

Abstract

Introduction: Our previous work indicated that the activation of the Toll-like receptor (TLR) 4 signaling pathway contributed to noise-induced cochlear inflammation. Previous studies have reported that low-molecular-weight hyaluronic acid (LMW-HA) accumulates during aseptic trauma and promotes inflammation by activating the TLR4 signaling pathway. We hypothesized that LMW-HA or enzymes synthesizing or degrading HA might be involved in noise-induced cochlear inflammation.

Methods: The present study included two arms. The first arm was the noise exposure study, in which TLR4, proinflammatory cytokines, HA, hyaluronic acid synthases (HASs), and hyaluronidases (HYALs) in the cochlea as well as auditory brainstem response (ABR) thresholds were measured before and after noise exposure. The second arm was analysis of HA delivery-induced reactions, in which control solution, high-molecular-weight HA (HMW-HA), or LMW-HA was delivered into the cochlea by cochleostomy or intratympanic injection. Then, the ABR threshold and cochlear inflammation were measured.

Results: After noise exposure, the expression of TLR4, proinflammatory cytokines, HAS1, and HAS3 in the cochlea significantly increased over the 3rd to 7th day post-noise exposure (PE3, PE7). The expression of HYAL2 and HYAL3 dramatically decreased immediately after noise exposure, gradually increased thereafter to levels significantly greater than the preexposure level on PE3, and then rapidly returned to the preexposure level on PE7. The expression of HA, HAS2, and HYAL1 in the cochlea remained unchanged after exposure. After cochleostomy or intratympanic injection, both the hearing threshold shifts and the expression of TLR4, TNF-α, and IL-1β in the cochleae of the LMW-HA group were obviously greater than those of the control group and HMW-HA group. The expression of proinflammatory cytokines in the LMW-HA and control groups on the 7th day (D7) after cochleostomy tended to increase compared to that on the 3rd day (D3), whereas levels in the HMW-HA group tended to decrease on D7 compared to D3.

Conclusion: HAS1, HAS3, HYAL2, and HYAL3 in the cochlea are involved in acoustic trauma-induced cochlear inflammation through the potential proinflammatory function of LMW-HA.

Keywords: Cochlea; Hyaluronic acid; Inflammation; Noise-induced hearing loss.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Auditory Threshold
Cochlea
Cytokines / metabolism
Hearing Loss, Noise-Induced*
Humans
Hyaluronic Acid* / metabolism
Inflammation / metabolism
Toll-Like Receptor 4 / metabolism

Substances

Hyaluronic Acid
Toll-Like Receptor 4
Cytokines