Inhibition of inducible nitric oxide synthase protects against liver injury induced by mycobacterial infection and endotoxins.

Détails

ID Serval
serval:BIB_D74DF213FCDF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Inhibition of inducible nitric oxide synthase protects against liver injury induced by mycobacterial infection and endotoxins.
Périodique
Journal of Hepatology
Auteur(s)
Guler R., Olleros M.L., Vesin D., Parapanov R., Vesin C., Kantengwa S., Rubbia-Brandt L., Mensi N., Angelillo-Scherrer A., Martinez-Soria E., Tacchini-Cottier F., Garcia I.
ISSN
0168-8278 (Print)
ISSN-L
0168-8278
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
41
Numéro
5
Pages
773-781
Langue
anglais
Résumé
BACKGROUND/AIMS: Bacillus Calmette Guerin (BCG) infection causes hepatic injury following granuloma formation and secretion of cytokines which render mice highly sensitive to endotoxin-mediated hepatotoxicity. This work investigates the role of inducible nitric oxide synthase (iNOS) in liver damage induced by BCG and endotoxins in BCG-infected mice.
METHODS: Liver injury and cytokine activation induced by BCG and by LPS upon BCG infection (BCG/LPS) were compared in wild-type and iNOS-/- mice.
RESULTS: iNOS-/- mice infected with living BCG are protected from hepatic injury when compared to wild-type mice which express iNOS protein in macrophages forming hepatic granulomas. In addition, iNOS-/- mice show a decrease in BCG-induced IFN-gamma serum levels. LPS challenge in BCG-infected mice strongly activates iNOS in the liver and spleen of wild-type mice which show important liver damage associated with a dramatic increase in TNF and IL-6 and also Th1 type cytokines. In contrast, iNOS-/- mice are protected from liver injury after BCG/LPS challenge and their TNF, IL-6 and Th1 type cytokine serum levels raise moderately.
CONCLUSIONS: These results demonstrate that nitric oxide (NO) from iNOS is involved in hepatotoxicity induced by both mycobacterial infection and endotoxin effects upon BCG infection and that inhibition of NO from iNOS protects from liver injuries.
Mots-clé
Animals, Interleukin-6/metabolism, Lipopolysaccharides/pharmacology, Liver/enzymology, Liver Diseases/immunology, Liver Diseases/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium bovis, Nitric Oxide/metabolism, Nitric Oxide Synthase/genetics, Nitric Oxide Synthase/metabolism, Nitric Oxide Synthase Type II, Spleen/enzymology, Th1 Cells/metabolism, Tuberculosis/immunology, Tuberculosis/metabolism, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 16:08
Dernière modification de la notice
20/08/2019 16:57
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