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Jun N-terminal protein kinase enhances middle ear mucosal proliferation during bacterial otitis media

Furukawa, Masayuki; Ebmeyer, Joerg; Pak, Kwang; Austin, Darrell A.; Melhus, Åsa LU ; Webster, Nicholas J. G. and Ryan, Allen F. (2007) In Infection and Immunity 75(5). p.2562-2571
Abstract
Mucosal hyperplasia is a characteristic component of otitis media. The present study investigated the participation of signaling via the Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase in middle ear mucosal hyperplasia in animal models of bacterial otitis media. Otitis media was induced by the inoculation of nontypeable Haemophilus influenzae into the middle ear cavity. Western blotting revealed that phosphorylation of JNK isoforms in the middle ear mucosa preceded but paralleled mucosal hyperplasia in this in vivo rat model. Nuclear JNK phosphorylation was observed in many cells of both the mucosal epithelium and stroma by immunohistochemistry. In an in vitro model of primary rat middle ear mucosal explants,... (More)
Mucosal hyperplasia is a characteristic component of otitis media. The present study investigated the participation of signaling via the Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase in middle ear mucosal hyperplasia in animal models of bacterial otitis media. Otitis media was induced by the inoculation of nontypeable Haemophilus influenzae into the middle ear cavity. Western blotting revealed that phosphorylation of JNK isoforms in the middle ear mucosa preceded but paralleled mucosal hyperplasia in this in vivo rat model. Nuclear JNK phosphorylation was observed in many cells of both the mucosal epithelium and stroma by immunohistochemistry. In an in vitro model of primary rat middle ear mucosal explants, bacterially induced mucosal growth was blocked by the Rac/Cdc42 inhibitor Clostridium difficile toxin B, the mixed-lineage kinase inhibitor CEP11004, and the JNK inhibitor SP600125. Finally, the JNK inhibitor SP600125 significantly inhibited mucosal hyperplasia during in vivo bacterial otitis media in guinea pigs. Inhibition of JNK in vivo resulted in a diminished proliferative response, as shown by a local decrease in proliferating cell nuclear antigen protein expression by immunohistochemistry. We conclude that activation of JNK is a critical pathway for bacterially induced mucosal hyperplasia during otitis media, influencing tissue proliferation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
75
issue
5
pages
2562 - 2571
publisher
American Society for Microbiology
external identifiers
  • wos:000246345000055
  • scopus:34248370548
ISSN
1098-5522
DOI
10.1128/IAI.01656-06
language
English
LU publication?
yes
id
a00dabe6-cdbe-4e7d-99a7-7122e684106a (old id 660484)
date added to LUP
2007-12-11 14:33:59
date last changed
2017-01-01 05:10:17
@article{a00dabe6-cdbe-4e7d-99a7-7122e684106a,
  abstract     = {Mucosal hyperplasia is a characteristic component of otitis media. The present study investigated the participation of signaling via the Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase in middle ear mucosal hyperplasia in animal models of bacterial otitis media. Otitis media was induced by the inoculation of nontypeable Haemophilus influenzae into the middle ear cavity. Western blotting revealed that phosphorylation of JNK isoforms in the middle ear mucosa preceded but paralleled mucosal hyperplasia in this in vivo rat model. Nuclear JNK phosphorylation was observed in many cells of both the mucosal epithelium and stroma by immunohistochemistry. In an in vitro model of primary rat middle ear mucosal explants, bacterially induced mucosal growth was blocked by the Rac/Cdc42 inhibitor Clostridium difficile toxin B, the mixed-lineage kinase inhibitor CEP11004, and the JNK inhibitor SP600125. Finally, the JNK inhibitor SP600125 significantly inhibited mucosal hyperplasia during in vivo bacterial otitis media in guinea pigs. Inhibition of JNK in vivo resulted in a diminished proliferative response, as shown by a local decrease in proliferating cell nuclear antigen protein expression by immunohistochemistry. We conclude that activation of JNK is a critical pathway for bacterially induced mucosal hyperplasia during otitis media, influencing tissue proliferation.},
  author       = {Furukawa, Masayuki and Ebmeyer, Joerg and Pak, Kwang and Austin, Darrell A. and Melhus, Åsa and Webster, Nicholas J. G. and Ryan, Allen F.},
  issn         = {1098-5522},
  language     = {eng},
  number       = {5},
  pages        = {2562--2571},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {Jun N-terminal protein kinase enhances middle ear mucosal proliferation during bacterial otitis media},
  url          = {http://dx.doi.org/10.1128/IAI.01656-06},
  volume       = {75},
  year         = {2007},
}