Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury

DSpace/Manakin Repository

Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury

Citable link to this page


Title: Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury
Author: Dolinay, Tamás; Kaminski, Naftali; Ifedigbo, Emeka; Kaynar, A. Murat; Szilasi, Mária; Watkins, Simon C.; Hoetzel, Alexander; Wu, Wei; Ryter, Stefan W.; Choi, Augustine M.K.

Note: Order does not necessarily reflect citation order of authors.

Citation: Dolinay, Tamás, Wei Wu, Naftali Kaminski, Emeka Ifedigbo, A. Murat Kaynar, Mária Szilasi, Simon C. Watkins, Stefan W. Ryter, Alexander Hoetzel, and Augustine M. K. Choi. 2008. Mitogen-activated protein kinases regulate susceptibility to ventilator-induced lung injury. PLoS ONE 3(2): e1601.
Full Text & Related Files:
Abstract: Background: Mechanical ventilation causes ventilator-induced lung injury in animals and humans. Mitogen-activated protein kinases have been implicated in ventilator-induced lung injury though their functional significance remains incomplete. We characterize the role of p38 mitogen-activated protein kinase/mitogen activated protein kinase kinase-3 and c-Jun-NH2-terminal kinase-1 in ventilator-induced lung injury and investigate novel independent mechanisms contributing to lung injury during mechanical ventilation. Methodology and Principle Findings: C57/BL6 wild-type mice and mice genetically deleted for mitogen-activated protein kinase kinase-3 (mkk-3−/−) or c-Jun-NH2-terminal kinase-1 (jnk1−/−) were ventilated, and lung injury parameters were assessed. We demonstrate that mkk3−/− or jnk1−/− mice displayed significantly reduced inflammatory lung injury and apoptosis relative to wild-type mice. Since jnk1−/− mice were highly resistant to ventilator-induced lung injury, we performed comprehensive gene expression profiling of ventilated wild-type or jnk1−/− mice to identify novel candidate genes which may play critical roles in the pathogenesis of ventilator-induced lung injury. Microarray analysis revealed many novel genes differentially expressed by ventilation including matrix metalloproteinase-8 (MMP8) and GADD45α. Functional characterization of MMP8 revealed that mmp8−/− mice were sensitized to ventilator-induced lung injury with increased lung vascular permeability. Conclusions: We demonstrate that mitogen-activated protein kinase pathways mediate inflammatory lung injury during ventilator-induced lung injury. C-Jun-NH2-terminal kinase was also involved in alveolo-capillary leakage and edema formation, whereas MMP8 inhibited alveolo-capillary protein leakage.
Published Version: doi:10.1371/journal.pone.0001601
Other Sources:
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at
Citable link to this page:
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search