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IL-1β promotes glutamate excitotoxicity: indications for the link between inflammatory and synaptic vesicle cycle in

Na Zhang1,2,3, Yongdong Song1,2,3, Hanyue Wang1,3

  • 1Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, Shandong, China.

Cell Death Discovery
|November 20, 2024
PubMed

Insights

Interleukin-1 beta (IL-1β) elevates glutamate in Ménière

Area of Science:

  • Inner ear disorders
  • Neuroimmunology
  • Otolaryngology

Background:

  • Ménière's disease (MD) pathogenesis involves immune mechanisms.
  • Previous studies linked IL-1β to pyroptosis and endolymphatic hydrops severity.
  • The precise role of IL-1β in MD symptoms was previously unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms linking IL-1β to Ménière's disease.
  • To identify protein changes in the vestibular end organs (VO) and endolymphatic sac (ES) of MD patients.
  • To explore the role of glutamate metabolism in MD.

Main Methods:

  • Mass spectrometry analysis of VO and ES protein signatures in MD patients.
  • Gene ontology and protein pathway analysis.
  • In vitro studies using HEI-OC1 cells to assess IL-1β effects on Glutaminase (GLS).
  • In vivo studies using a mouse model of endolymphatic hydrops.

Main Results:

  • Differentially expressed proteins in ES were linked to adhesion; VO proteins were linked to synapse processes.
  • Elevated Glutaminase (GLS) expression was observed in the VO of MD patients.
  • IL-1β upregulated GLS, increasing glutamate levels in HEI-OC1 cells.
  • GLS inhibition or IL-1β receptor antagonism ameliorated auditory-vestibular dysfunction and reduced glutamate in mice.

Conclusions:

  • Imbalanced neurotransmitter release and immune responses are implicated in MD pathology.
  • Elevated glutamate, mediated by IL-1β and GLS, contributes to MD symptoms like hearing loss and vertigo.
  • Targeting glutamate pathways and IL-1β signaling offers potential therapeutic strategies for MD.

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