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J Immunol. 2005 Oct 15;175(8):4834-8.

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

Author information

1
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.

Erratum in

  • J Immunol. 2005 Dec 15;175(12):8440.

Abstract

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.

PMID:
16210584
DOI:
10.4049/jimmunol.175.8.4834
[Indexed for MEDLINE]
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