Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury
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 signa...
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Online Access: | https://biblio.ugent.be/publication/2976377 http://hdl.handle.net/1854/LU-2976377 https://doi.org/10.1016/j.cell.2008.02.043 https://biblio.ugent.be/publication/2976377/file/2976404 |
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ftunivgent:oai:archive.ugent.be:2976377 2023-10-01T03:54:50+02:00 Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury Imai, Yumiko Kuba, Keiji Neely, G Greg Yaghubian-Malhami, Rubina Perkmann, Thomas van Loo, Geert Ermolaeva, Maria Veldhuizen, Ruud Leung, YH Connie Wang, Hongliang Liu, Haolin Sun, Yang Pasparakis, Manolis Kopf, Manfred Mech, Christin Bavari, Sina Peiris, JS Malik Slutsky, Arthur S Akira, Shizuo Hultqvist, Malin Holmdahl, Rikard Nicholls, John Jiang, Chengyu Binder, Christoph J Penninger, Josef M 2008 application/pdf https://biblio.ugent.be/publication/2976377 http://hdl.handle.net/1854/LU-2976377 https://doi.org/10.1016/j.cell.2008.02.043 https://biblio.ugent.be/publication/2976377/file/2976404 eng eng https://biblio.ugent.be/publication/2976377 http://hdl.handle.net/1854/LU-2976377 http://dx.doi.org/10.1016/j.cell.2008.02.043 https://biblio.ugent.be/publication/2976377/file/2976404 No license (in copyright) info:eu-repo/semantics/restrictedAccess CELL ISSN: 0092-8674 Biology and Life Sciences APOPTOTIC CELLS SYNCYTIAL VIRUS APOLIPOPROTEIN-E PULMONARY SURFACTANT FACTOR-KAPPA-B 1918 PANDEMIC VIRUS LOW-DENSITY-LIPOPROTEIN RESPIRATORY-DISTRESS-SYNDROME TRANSCRIPTION FACTORS OXIDIZED PHOSPHOLIPIDS journalArticle info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2008 ftunivgent https://doi.org/10.1016/j.cell.2008.02.043 2023-09-06T22:32:12Z 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. Article in Journal/Newspaper Avian flu Ghent University Academic Bibliography Cell 133 2 235 249 |
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Open Polar |
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Ghent University Academic Bibliography |
op_collection_id |
ftunivgent |
language |
English |
topic |
Biology and Life Sciences APOPTOTIC CELLS SYNCYTIAL VIRUS APOLIPOPROTEIN-E PULMONARY SURFACTANT FACTOR-KAPPA-B 1918 PANDEMIC VIRUS LOW-DENSITY-LIPOPROTEIN RESPIRATORY-DISTRESS-SYNDROME TRANSCRIPTION FACTORS OXIDIZED PHOSPHOLIPIDS |
spellingShingle |
Biology and Life Sciences APOPTOTIC CELLS SYNCYTIAL VIRUS APOLIPOPROTEIN-E PULMONARY SURFACTANT FACTOR-KAPPA-B 1918 PANDEMIC VIRUS LOW-DENSITY-LIPOPROTEIN RESPIRATORY-DISTRESS-SYNDROME TRANSCRIPTION FACTORS OXIDIZED PHOSPHOLIPIDS Imai, Yumiko Kuba, Keiji Neely, G Greg Yaghubian-Malhami, Rubina Perkmann, Thomas van Loo, Geert Ermolaeva, Maria Veldhuizen, Ruud Leung, YH Connie Wang, Hongliang Liu, Haolin Sun, Yang Pasparakis, Manolis Kopf, Manfred Mech, Christin Bavari, Sina Peiris, JS Malik Slutsky, Arthur S Akira, Shizuo Hultqvist, Malin Holmdahl, Rikard Nicholls, John Jiang, Chengyu Binder, Christoph J Penninger, Josef M Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury |
topic_facet |
Biology and Life Sciences APOPTOTIC CELLS SYNCYTIAL VIRUS APOLIPOPROTEIN-E PULMONARY SURFACTANT FACTOR-KAPPA-B 1918 PANDEMIC VIRUS LOW-DENSITY-LIPOPROTEIN RESPIRATORY-DISTRESS-SYNDROME TRANSCRIPTION FACTORS OXIDIZED PHOSPHOLIPIDS |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Imai, Yumiko Kuba, Keiji Neely, G Greg Yaghubian-Malhami, Rubina Perkmann, Thomas van Loo, Geert Ermolaeva, Maria Veldhuizen, Ruud Leung, YH Connie Wang, Hongliang Liu, Haolin Sun, Yang Pasparakis, Manolis Kopf, Manfred Mech, Christin Bavari, Sina Peiris, JS Malik Slutsky, Arthur S Akira, Shizuo Hultqvist, Malin Holmdahl, Rikard Nicholls, John Jiang, Chengyu Binder, Christoph J Penninger, Josef M |
author_facet |
Imai, Yumiko Kuba, Keiji Neely, G Greg Yaghubian-Malhami, Rubina Perkmann, Thomas van Loo, Geert Ermolaeva, Maria Veldhuizen, Ruud Leung, YH Connie Wang, Hongliang Liu, Haolin Sun, Yang Pasparakis, Manolis Kopf, Manfred Mech, Christin Bavari, Sina Peiris, JS Malik Slutsky, Arthur S Akira, Shizuo Hultqvist, Malin Holmdahl, Rikard Nicholls, John Jiang, Chengyu Binder, Christoph J Penninger, Josef M |
author_sort |
Imai, Yumiko |
title |
Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury |
title_short |
Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury |
title_full |
Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury |
title_fullStr |
Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury |
title_full_unstemmed |
Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury |
title_sort |
identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury |
publishDate |
2008 |
url |
https://biblio.ugent.be/publication/2976377 http://hdl.handle.net/1854/LU-2976377 https://doi.org/10.1016/j.cell.2008.02.043 https://biblio.ugent.be/publication/2976377/file/2976404 |
genre |
Avian flu |
genre_facet |
Avian flu |
op_source |
CELL ISSN: 0092-8674 |
op_relation |
https://biblio.ugent.be/publication/2976377 http://hdl.handle.net/1854/LU-2976377 http://dx.doi.org/10.1016/j.cell.2008.02.043 https://biblio.ugent.be/publication/2976377/file/2976404 |
op_rights |
No license (in copyright) info:eu-repo/semantics/restrictedAccess |
op_doi |
https://doi.org/10.1016/j.cell.2008.02.043 |
container_title |
Cell |
container_volume |
133 |
container_issue |
2 |
container_start_page |
235 |
op_container_end_page |
249 |
_version_ |
1778522811283800064 |