| First Author | Zhang X | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 8 | Pages | 4834-8 |
| PubMed ID | 16210584 | Mgi Jnum | J:119056 |
| Mgi Id | MGI:3701057 | Doi | 10.4049/jimmunol.175.8.4834 |
| Citation | Zhang X, et al. (2005) Cutting edge: TLR4 deficiency confers susceptibility to lethal oxidant lung injury. J Immunol 175(8):4834-8 |
| abstractText | 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. |
