MCMV triggers ROS/NLRP3-associated inflammasome activation in the inner ear of mice and cultured spiral ganglion neurons, contributing to sensorineural hearing loss

Int J Mol Med. 2018 Jun;41(6):3448-3456. doi: 10.3892/ijmm.2018.3539. Epub 2018 Mar 6.

Abstract

Congenital cytomegalovirus (CMV) infection is the most common infectious cause of sensorineural hearing loss in children. While the importance of CMV‑induced SNHL has been described, the mechanisms underlying its pathogenesis and the role of inflammatory responses remain elusive. The present study established an experimental model of hearing loss after systemic infection with murine CMV (MCMV) in newborn mice. Auditory brainstem responses were tested to evaluate hearing at 3 weeks, expression of inflammasome‑-associated factors was assessed by immunofluorescence, western blot analysis, reverse transcription‑quantitative polymerase chain reaction and ELISA. MCMV sequentially induced inflammasome‑associated factors. Furthermore, the inflammasome‑associated factors were also increased in cultured spiral ganglion neurons infected with MCMV for 24 h. In addition, MCMV increased the content of reactive oxygen species (ROS). These results suggest that hearing loss caused by MCMV infection may be associated with ROS‑induced inflammation.

MeSH terms

  • Animals
  • Cells, Cultured
  • Ear, Inner / cytology
  • Ear, Inner / physiology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique
  • Hearing Loss / physiopathology
  • Inflammasomes / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Reactive Oxygen Species / metabolism
  • Spiral Ganglion / cytology*

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species