Cutting edge: TLR4 deficiency confers susceptibility to lethal oxidant lung injury.


Journal Article

TLRs have been studied extensively in pathogen-mediated host responses. We use a murine model of lethal oxidant-mediated injury to demonstrate for the first time that mammalian TLR4 is required for survival and lung integrity. Administering high levels of inspired oxygen, or hyperoxia, is commonly used as a life-sustaining measure in critically ill patients. However, prolonged exposures can lead to respiratory failure and death. TLR4-deficient mice exhibited increased mortality and lung injury during hyperoxia. The enhanced susceptibility of TLR4-deficient mice to hyperoxia was associated with an inability to up-regulate Bcl-2 and phospho-Akt. Restoration of Bcl-2 and phospho-Akt levels by the exogenous transfer of the antioxidant gene heme oxygenase-1 markedly attenuated hyperoxia-induced injury, apoptosis, and mortality in TLR4-deficient mice. Taken together, our results suggest a protective role of TLR4 in oxidant-mediated injury, providing novel mechanistic links among innate immunity, oxidant stress, and apoptosis.

Full Text

Duke Authors

Cited Authors

  • Zhang, X; Shan, P; Qureshi, S; Homer, R; Medzhitov, R; Noble, PW; Lee, PJ

Published Date

  • October 15, 2005

Published In

Volume / Issue

  • 175 / 8

Start / End Page

  • 4834 - 4838

PubMed ID

  • 16210584

Pubmed Central ID

  • 16210584

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.175.8.4834


  • eng

Conference Location

  • United States