| First Author | Singh N | Year | 2012 |
| Journal | Mol Immunol | Volume | 50 |
| Issue | 4 | Pages | 244-52 |
| PubMed ID | 22364946 | Mgi Jnum | J:182739 |
| Mgi Id | MGI:5316529 | Doi | 10.1016/j.molimm.2012.01.011 |
| Citation | Singh N, et al. (2012) Reduced oxidative tissue damage during endotoxemia in IRAK-1 deficient mice. Mol Immunol 50(4):244-52 |
| abstractText | The generation of reactive oxygen species (ROS) triggered by bacterial endotoxin lipopolysaccharide (LPS) plays a key role during the pathogenesis of sepsis. Given the key role that the interleukin-1 receptor associated kinase-1 (IRAK-1) plays in LPS-mediated Toll-like-receptor 4 (TLR4) pathway, we herein tested whether deletion of IRAK-1 gene in mice may render protection from LPS-induced oxidative tissue damage. In this report, we studied the levels of oxidative stress in vital organs including liver, kidney, and brain from wild type (WT) and IRAK-1 deficient mice injected with a lethal dose of LPS (25mg/kg), a TLR4-specific agonist. We demonstrated that LPS challenge induced marked elevation of lipid peroxidation and nitrite levels in the plasma and tissues of WT mice, as well as elevated pro-inflammatory mediators. In contrast, IRAK-1 deficient mice had significantly lower lipid peroxidation and nitrite levels, as well as lower levels of pro-inflammatory mediators. Mechanistically, LPS triggered higher levels of iNOS activity and elevated membrane translocation of p47(phox), a key component of NADPH oxidase in immune cell derived from WT mice compared to IRAK-1 deficient mice. Additionally, tissues harvested from WT mice injected with LPS exhibited reduced activities of anti-oxidant enzymes including glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD). In contrast, LPS challenge failed to reduce the activities of GPx and SOD in IRAK-1 deficient tissues. As a consequence, LPS caused significantly pronounced damage to liver and kidney tissues in WT mice as compared to IRAK-1 deficient mice. |
