| First Author | Botez G | Year | 2015 |
| Journal | Innate Immun | Volume | 21 |
| Issue | 6 | Pages | 609-18 |
| PubMed ID | 25956304 | Mgi Jnum | J:314049 |
| Mgi Id | MGI:6760212 | Doi | 10.1177/1753425915569367 |
| Citation | Botez G, et al. (2015) Age-dependent therapeutic effects of liver X receptor-alpha activation in murine polymicrobial sepsis. Innate Immun 21(6):609-18 |
| abstractText | The severity of sepsis is significantly affected by advanced age; however, age-dependent molecular mechanisms of this susceptibility are unknown. Nuclear liver X receptor-alpha (LXRalpha) is a regulator of lipid metabolism with associated anti-inflammatory properties. Here, we investigated the role of LXRalpha in age-dependent lung injury and outcome of sepsis. Male C57BL/6, LXRalpha-deficient (LXRalpha(-/-)) and wild type (WT) (LXRalpha(+/+)) mice of different ages were subjected to sepsis by cecal ligation and puncture (CLP). In pharmacological studies, treatment with the LXRalpha ligand T0901317 reduced lung neutrophil infiltration in C57BL/6 mice aged from 1 to 8 mo when compared with vehicle-treated animals subjected to CLP. The LXRalpha ligand improved survival in young mice (2-3 mo old) but did not affect survival or neutrophil infiltration in mature adult mice (11-13 mo old). Immunoblotting revealed an age-dependent decrease of lung LXRalpha levels. Young LXRalpha(-/-) mice (2-3 mo old) exhibited earlier mortality than age-matched WT mice after CLP. Lung damage and neutrophil infiltration, lung activation of the pro-inflammatory NF-kappaB and plasma IL-6 levels were higher in LXRalpha(-/-) mice 18 h after CLP compared with LXRalpha(+/+) mice. This study suggests that the anti-inflammatory properties of LXRalpha in sepsis are age-dependent and severely compromised in mature adult animals. |
