| First Author | Goodwin JE | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 10 | Pages | e108126 |
| PubMed ID | 25299055 | Mgi Jnum | J:223570 |
| Mgi Id | MGI:5649509 | Doi | 10.1371/journal.pone.0108126 |
| Citation | Goodwin JE, et al. (2014) Loss of the endothelial glucocorticoid receptor prevents the therapeutic protection afforded by dexamethasone after LPS. PLoS One 9(10):e108126 |
| abstractText | Glucocorticoids are normally regarded as anti-inflammatory therapy for a wide variety of conditions and have been used with some success in treating sepsis and sepsis-like syndromes. We previously demonstrated that mice lacking the glucocorticoid receptor in the endothelium (GR EC KO mice) are extremely sensitive to low-dose LPS and demonstrate prolonged activation and up regulation of NF-kappaB. In this study we pre-treated these GR EC KO mice with dexamethasone and assessed their response to an identical dose of LPS. Surprisingly, the GR EC KO mice fared even worse than when given LPS alone demonstrating increased mortality, increased levels of the inflammatory cytokines TNF-alpha and IL-6 and increased nitric oxide release after the dexamethasone pre-treatment. As expected, control animals pre-treated with dexamethasone showed improvement in all parameters assayed. Mechanistically we demonstrate that GR EC KO mice show increased iNOS production and NF-kappaB activation despite treatment with dexamethasone. |
