PMID- 17452470
OWN - NLM
STAT- MEDLINE
DCOM- 20070807
LR  - 20220408
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 75
IP  - 7
DP  - 2007 Jul
TI  - Toll-like receptor 2-dependent NF-kappaB activation is involved in nontypeable 
      Haemophilus influenzae-induced monocyte chemotactic protein 1 up-regulation in 
      the spiral ligament fibrocytes of the inner ear.
PG  - 3361-72
AB  - Inner ear dysfunction secondary to chronic otitis media (OM), including 
      high-frequency sensorineural hearing loss or vertigo, is not uncommon. Although 
      chronic middle ear inflammation is believed to cause inner ear dysfunction by 
      entry of OM pathogen components or cytokines from the middle ear into the inner 
      ear, the underlying mechanisms are not well understood. Previously, we 
      demonstrated that the spiral ligament fibrocyte (SLF) cell line up-regulates 
      monocyte chemotactic protein 1 (MCP-1) expression after treatment with 
      nontypeable Haemophilus influenzae (NTHI), one of the most common OM pathogens. 
      We hypothesized that the SLF-derived MCP-1 plays a role in inner ear inflammation 
      secondary to OM that is responsible for hearing loss and dizziness. The purpose 
      of this study was to investigate the signaling pathway involved in NTHI-induced 
      MCP-1 up-regulation in SLFs. Here we show for the first time that NTHI induces 
      MCP-1 up-regulation in the SLFs via Toll-like receptor 2 (TLR2)-dependent 
      activation of NF-kappaB. TLR2(-/-)- and MyD88(-/-)-derived SLFs revealed 
      involvement of TLR2 and MyD88 in NTHI-induced MCP-1 up-regulation. Studies using 
      chemical inhibitors and dominant-negative constructs demonstrated that it is 
      mediated by the IkappaKbeta-dependent IkappaBalpha phosphorylation and 
      NTHI-induced NF-kappaB nuclear translocation. Furthermore, we demonstrated that 
      the binding of NF-kappaB to the enhancer region of MCP-1 is involved in this 
      up-regulation. In addition, we have identified a potential NF-kappaB motif that 
      is responsive and specific to certain NTHI molecules or ligands. Further studies 
      are necessary to reveal specific ligands of NTHI that activate host receptors. 
      These results may provide us with new therapeutic strategies for prevention of 
      inner ear dysfunction secondary to chronic middle ear inflammation.
FAU - Moon, Sung K
AU  - Moon SK
AD  - The Gonda Department of Cell and Molecular Biology, House Ear Institute, 2100 
      West 3rd Street, Los Angeles, CA 90057, USA.
FAU - Woo, Jeong-Im
AU  - Woo JI
FAU - Lee, Haa-Yung
AU  - Lee HY
FAU - Park, Raekil
AU  - Park R
FAU - Shimada, Jun
AU  - Shimada J
FAU - Pan, Huiqi
AU  - Pan H
FAU - Gellibolian, Robert
AU  - Gellibolian R
FAU - Lim, David J
AU  - Lim DJ
LA  - eng
GR  - P30 DC 006276-04/DC/NIDCD NIH HHS/United States
GR  - R03 DC008696/DC/NIDCD NIH HHS/United States
GR  - P30 DC006276/DC/NIDCD NIH HHS/United States
GR  - R03 DC008696-01A1/DC/NIDCD NIH HHS/United States
GR  - 5R01 DC 005025-05/DC/NIDCD NIH HHS/United States
GR  - R01 DC005025/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070423
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 2)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Cell Line, Transformed
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Child, Preschool
MH  - Ear, Inner/*cytology/immunology/microbiology
MH  - Fibroblasts/immunology/*microbiology
MH  - Haemophilus influenzae/isolation & purification/*pathogenicity
MH  - Humans
MH  - Ligaments/cytology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/genetics/*metabolism
MH  - Otitis Media/microbiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spiral Ganglion
MH  - Spiral Lamina
MH  - Toll-Like Receptor 2/*metabolism
MH  - *Up-Regulation
PMC - PMC1932924
EDAT- 2007/04/25 09:00
MHDA- 2007/08/08 09:00
PMCR- 2007/11/01
CRDT- 2007/04/25 09:00
PHST- 2007/04/25 09:00 [pubmed]
PHST- 2007/08/08 09:00 [medline]
PHST- 2007/04/25 09:00 [entrez]
PHST- 2007/11/01 00:00 [pmc-release]
AID - IAI.01886-06 [pii]
AID - 1886-06 [pii]
AID - 10.1128/IAI.01886-06 [doi]
PST - ppublish
SO  - Infect Immun. 2007 Jul;75(7):3361-72. doi: 10.1128/IAI.01886-06. Epub 2007 Apr 
      23.