Activation of TRAIL-DR5 pathway promotes sensorineural degeneration in the inner ear

Shyan-Yuan Kao; Vitor Y R Soares; Arthur G Kristiansen; Konstantina M Stankovic

doi:10.1111/acel.12437

Activation of TRAIL-DR5 pathway promotes sensorineural degeneration in the inner ear

Aging Cell. 2016 Apr;15(2):301-8. doi: 10.1111/acel.12437. Epub 2016 Jan 21.

Authors

Shyan-Yuan Kao¹, Vitor Y R Soares^{1

2}, Arthur G Kristiansen¹, Konstantina M Stankovic^{1

2

3}

Affiliations

¹ Eaton Peabody Laboratories and Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
² Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.
³ Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA, USA.

Abstract

Tumor necrosis factor (TNF) family cytokines are important mediators of inflammation. Elevated levels of serum TNF-α are associated with human sensorineural hearing loss via poorly understood mechanisms. We demonstrate, for the first time, expression of TNF-related apoptosis-inducing ligand (TRAIL) and its signaling death receptor 5 (DR5) in the murine inner ear and show that exogenous TRAIL can trigger hair cell and neuronal degeneration, which can be partly prevented with DR5-blocking antibodies.

Keywords: DR5; OPG; TRAIL; cochlea; hair cells; spiral ganglion neuron.

Publication types

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

MeSH terms

Animals
Cochlea / metabolism
Cochlea / pathology
Ear, Inner / metabolism
Ear, Inner / pathology
Hair Cells, Auditory, Inner / metabolism*
Hair Cells, Auditory, Inner / pathology
Hearing Loss, Sensorineural / genetics
Hearing Loss, Sensorineural / metabolism*
Hearing Loss, Sensorineural / therapy
Immunohistochemistry
In Situ Hybridization, Fluorescence
Mice
Mice, Inbred C57BL
Receptors, TNF-Related Apoptosis-Inducing Ligand / biosynthesis
Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism*
Recombinant Proteins / pharmacology
Signal Transduction
Spiral Ganglion / metabolism
Spiral Ganglion / pathology
TNF-Related Apoptosis-Inducing Ligand / genetics
TNF-Related Apoptosis-Inducing Ligand / metabolism*
TNF-Related Apoptosis-Inducing Ligand / pharmacology

Substances

Receptors, TNF-Related Apoptosis-Inducing Ligand
Recombinant Proteins
TNF-Related Apoptosis-Inducing Ligand
Tnfsf10 protein, mouse