PMID- 27253409
OWN - NLM
STAT- MEDLINE
DCOM- 20171009
LR  - 20181113
IS  - 2041-4889 (Electronic)
VI  - 7
IP  - 6
DP  - 2016 Jun 2
TI  - Toll-like receptor 4 modulates the cochlear immune response to acoustic injury.
PG  - e2245
LID - 10.1038/cddis.2016.156 [doi]
AB  - Acoustic overstimulation traumatizes the cochlea, resulting in auditory 
      dysfunction. As a consequence of acoustic injury, the immune system in the 
      cochlea is activated, leading to the production of inflammatory mediators and the 
      infiltration of immune cells. However, the molecular mechanisms responsible for 
      initiating these immune responses remain unclear. Here, we investigate the 
      functional role of Toll-like receptor 4 (Tlr4), a cellular receptor that 
      activates the innate immune system, in the regulation of cochlear responses to 
      acoustic overstimulation. Using a Tlr4 knockout mouse model, we examined how Tlr4 
      deficiency affects sensory cell pathogenesis, auditory dysfunction and cochlear 
      immune activity. We demonstrate that Tlr4 knockout does not affect sensory cell 
      viability under physiological conditions, but reduces the level of sensory cell 
      damage and cochlear dysfunction after acoustic injury. Together, these findings 
      suggest that Tlr4 promotes sensory cell degeneration and cochlear dysfunction 
      after acoustic injury. Acoustic injury provokes a site-dependent inflammatory 
      response in both the organ of Corti and the tissues of the lateral wall and 
      basilar membrane. Tlr4 deficiency affects these inflammatory responses in a 
      site-dependent manner. In the organ of Corti, loss of Tlr4 function suppresses 
      the production of interleukin 6 (Il6), a pro-inflammatory molecule, after 
      acoustic injury. By contrast, the production of inflammatory mediators, including 
      Il6, persists in the lateral wall and basilar membrane. In addition to immune 
      molecules, Tlr4 knockout inhibits the expression of major histocompatibility 
      complex class II, an antigen-presenting molecule, in macrophages, suggesting that 
      Tlr4 participates in the antigen-presenting function of macrophages after 
      acoustic trauma. Together, these results suggest that Tlr4 regulates multiple 
      aspects of the immune response in the cochlea and contributes to cochlear 
      pathogenesis after acoustic injury.
FAU - Vethanayagam, R R
AU  - Vethanayagam RR
AD  - Center for Hearing and Deafness, State University of New York at Buffalo, 137 
      Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA.
FAU - Yang, W
AU  - Yang W
AD  - Center for Hearing and Deafness, State University of New York at Buffalo, 137 
      Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA.
FAU - Dong, Y
AU  - Dong Y
AD  - Center for Hearing and Deafness, State University of New York at Buffalo, 137 
      Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA.
FAU - Hu, B H
AU  - Hu BH
AD  - Center for Hearing and Deafness, State University of New York at Buffalo, 137 
      Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA.
LA  - eng
GR  - R01 DC010154/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160602
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Toll-Like Receptor 4)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - Cochlea/*immunology/*pathology
MH  - Gene Expression Regulation
MH  - Hearing Loss, Noise-Induced/genetics/*immunology/*pathology
MH  - Histocompatibility Antigens Class II/metabolism
MH  - Inflammation/genetics/pathology
MH  - Inflammation Mediators/metabolism
MH  - Macrophages/metabolism/pathology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Monocytes/metabolism/pathology
MH  - Noise
MH  - Organ of Corti/metabolism/pathology
MH  - Ovalbumin
MH  - Toll-Like Receptor 4/deficiency/*metabolism
PMC - PMC5143385
EDAT- 2016/06/03 06:00
MHDA- 2017/10/11 06:00
PMCR- 2016/06/01
CRDT- 2016/06/03 06:00
PHST- 2016/02/19 00:00 [received]
PHST- 2016/04/29 00:00 [revised]
PHST- 2016/05/03 00:00 [accepted]
PHST- 2016/06/03 06:00 [entrez]
PHST- 2016/06/03 06:00 [pubmed]
PHST- 2017/10/11 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - cddis2016156 [pii]
AID - 10.1038/cddis.2016.156 [doi]
PST - epublish
SO  - Cell Death Dis. 2016 Jun 2;7(6):e2245. doi: 10.1038/cddis.2016.156.