| First Author | Glosli H | Year | 2002 |
| Journal | FASEB J | Volume | 16 |
| Issue | 11 | Pages | 1450-2 |
| PubMed ID | 12205044 | Mgi Jnum | J:78636 |
| Mgi Id | MGI:2385574 | Doi | 10.1096/fj.01-0948fje |
| Citation | Glosli H, et al. (2002) Human TNF-alpha in transgenic mice induces differential changes in redox status and glutathione-regulating enzymes. FASEB J 16(11):1450-2 |
| abstractText | Tumor necrosis factor a (TNF-alpha) is a pleiotropic cytokine involved in several diseases. Various effects of TNF-alpha are mediated by the induction of a cellular state consistent with oxidative stress. Glutathione (GSH) is a major redox-buffer of eukaryotic cells and is important in the defense against oxidative stress. We hypothesized that persistent TNF-alpha secretion could induce oxidative stress through modulation of GSH metabolism. This hypothesis was examined in a transgenic mouse model with low, persistent expression of human TNF-alpha in the T cell compartment. Major findings were i) marked tissue-specific changes in GSH redox status and GSH regulating enzymes, with the most pronounced changes in liver; ii) moderate changes in GSH metabolism and up-regulation of GSH-regulating enzymes were observed in lung and kidney from transgenic mice; and iii) liver, lung and kidney from transgenic mice had decreased levels of total glutathione, whereas splenic CD4+ and CD8+ T cells had a marked increase in oxidized glutathione as the major change. Oxidative stress induced by persistent low-grade exposure to TNF-alpha in transgenic mice appears to involve marked organ-specific alterations in glutathione redox status and glutathione-regulating enzymes with the most pronounced changes in the liver. These mice constitute a useful model for immunodeficiency syndromes and chronic inflammatory diseases involving pathogenic interaction between TNF-alpha and oxidative stress. |
