Advanced

Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury

Imai, Y.; Kuba, K.; Neely, G. G.; Yaghubian-Malhami, R.; Perkmann, T.; van Loo, G.; Ermolaeva, M.; Veldhuizen, R.; Leung, Y. H. C. and Wang, H. L., et al. (2008) In Cell 133(2). p.235-249
Abstract
Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression... (More)
Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
SYNCYTIAL VIRUS, PULMONARY SURFACTANT, APOLIPOPROTEIN-E, APOPTOTIC CELLS, 1918 PANDEMIC, RESPIRATORY-DISTRESS-SYNDROME, LOW-DENSITY-LIPOPROTEIN, OXIDIZED PHOSPHOLIPIDS, TRANSCRIPTION FACTORS, VIRUS, FACTOR-KAPPA-B
in
Cell
volume
133
issue
2
pages
235 - 249
publisher
Cell Press
external identifiers
  • wos:000255052000014
  • scopus:41949087380
ISSN
1097-4172
DOI
10.1016/j.cell.2008.02.043
language
English
LU publication?
yes
id
40658950-fe03-411f-92c9-baa37b332fc6 (old id 1423295)
date added to LUP
2009-06-16 11:56:14
date last changed
2017-09-17 04:55:55
@article{40658950-fe03-411f-92c9-baa37b332fc6,
  abstract     = {Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.},
  author       = {Imai, Y. and Kuba, K. and Neely, G. G. and Yaghubian-Malhami, R. and Perkmann, T. and van Loo, G. and Ermolaeva, M. and Veldhuizen, R. and Leung, Y. H. C. and Wang, H. L. and Liu, H. L. and Sun, Y. and Pasparakis, M. and Kopf, M. and Mech, C. and Bavari, S. and Peiris, J. S. M. and Slutsky, A. S. and Akira, S. and Hultqvist, Malin and Holmdahl, Rikard and Nicholls, J. and Jiang, C. Y. and Binder, C. J. and Penninger, J. M.},
  issn         = {1097-4172},
  keyword      = {SYNCYTIAL VIRUS,PULMONARY SURFACTANT,APOLIPOPROTEIN-E,APOPTOTIC CELLS,1918 PANDEMIC,RESPIRATORY-DISTRESS-SYNDROME,LOW-DENSITY-LIPOPROTEIN,OXIDIZED PHOSPHOLIPIDS,TRANSCRIPTION FACTORS,VIRUS,FACTOR-KAPPA-B},
  language     = {eng},
  number       = {2},
  pages        = {235--249},
  publisher    = {Cell Press},
  series       = {Cell},
  title        = {Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury},
  url          = {http://dx.doi.org/10.1016/j.cell.2008.02.043},
  volume       = {133},
  year         = {2008},
}