|
|
 |
 |
| |
 Printable version |
Regulation of lipopolysaccharide-induced NO synthase expression in the major organs in a mouse model. The roles of endogenous interferon-g, tumor nécrosis factor-a and interleukin-10. |
European Cytokine Network. Volume 11, Number 1, 39-46, March 2000, Articles originaux
|
 Free Article
|
Author(s) : J.C. ter Steege, W.C. van de Ven, P.Ph. Forget, W.A. Buurman |
Summary : Elevated NO production mediated by activation of the enzyme iNOS is thought to play a central role in the development of tissue damage observed during septic shock. IFN-g, TNF-a and IL-10 have been shown to be involved in the regulation of LPS-induced serum levels of the NO-oxidation products nitrate and nitrite. Therefore, in the present study, we investigated the role of endogenous IFN-g, TNF-a and IL-10 in the regulation of LPS-induced tissue iNOS expression in the major organs. To this end, mice were pre-treated with anti-IFN-g, anti-TNF-a, anti-IL-10 monoclonal antibodies, or combinations of these, two hours before intraperitoneal LPS-challenge. Immunohistochemical staining for iNOS and determination of iNOS activity indicated that iNOS expression was mainly upregulated in the small intestine, lung and heart, and that IFN-g, TNF-a as well as IL-10 are involved in the regulation of iNOS expression and enzyme activity. Whereas blocking either IFN-g or TNF-a did not affect iNOS expression, iNOS enzymatic activity seems to be inhibited. In contrast, blocking both mediators nearly completely prevents iNOS expression after LPS challenge, suggesting that the presence of either IFN-g or TNF-a is essential for LPS-induced iNOS expression in these organs. Combined treatment of these monoclonal antibodies revealed that whereas on the one hand IL-10 inhibits LPS-induced iNOS expression, on the other hand IL-10 or an IL-10 inducible factor is also involved in the upregulation of iNOS expression after LPS challenge. |
Keywords : IFN-g, IL-10, iNOS, LPS, mouse organs, TNF-a. |
|
