| First Author | Lubos E | Year | 2010 |
| Journal | FASEB J | Volume | 24 |
| Issue | 7 | Pages | 2525-32 |
| PubMed ID | 20219985 | Mgi Jnum | J:162352 |
| Mgi Id | MGI:4818740 | Doi | 10.1096/fj.09-147421 |
| Citation | Lubos E, et al. (2010) Glutathione peroxidase-1 modulates lipopolysaccharide-induced adhesion molecule expression in endothelial cells by altering CD14 expression. FASEB J 24(7):2525-32 |
| abstractText | CD14 contributes to LPS signaling in leukocytes through formation of toll-like receptor 4/CD14 receptor complexes; however, a specific role for endogenous cell-surface CD14 in endothelial cells is unclear. We have found that suppression of glutathione peroxidase-1 (GPx-1) in human microvascular endothelial cells increases CD14 gene expression compared to untreated or siControl (siCtrl)-treated conditions. Following LPS treatment, GPx-1 deficiency augmented LPS-induced intracellular reactive oxygen species accumulation, CD14 expression, and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression compared to LPS-treated control cells. GPx-1 deficiency also transiently augmented LPS-induced vascular cell adhesion molecule-1 (VCAM-1) expression. Adenoviral overexpression of GPx-1 significantly diminished LPS-mediated responses in adhesion molecule expression. Consistent with these findings, LPS responses were also greater in endothelial cells derived from GPx-1-knockout mice, whereas adhesion molecule expression was decreased in cells from GPx-1-overexpressing transgenic mice. Knockdown of CD14 attenuated LPS-mediated up-regulation of ICAM-1 and VCAM-1 mRNA and protein, and it mitigated the effects of GPx-1 deficiency on LPS-induced adhesion molecule expression. Taken together, these data suggest that GPx-1 modulates the endothelial cell response to LPS, in part, by altering CD14-mediated effects. |
