Dominant negative MyD88 proteins inhibit interleukin-1beta /interferon-gamma -mediated induction of nuclear factor kappa B-dependent nitrite production and apoptosis in beta cells.

Détails

ID Serval
serval:BIB_15809
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Dominant negative MyD88 proteins inhibit interleukin-1beta /interferon-gamma -mediated induction of nuclear factor kappa B-dependent nitrite production and apoptosis in beta cells.
Périodique
Journal of Biological Chemistry
Auteur(s)
Dupraz P., Cottet S., Hamburger F., Dolci W., Felley-Bosco E., Thorens B.
ISSN
0021-9258[print], 0021-9258[linking]
Statut éditorial
Publié
Date de publication
2000
Volume
275
Numéro
48
Pages
37672-37678
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Insulin-dependent diabetes mellitus is an autoimmune disease in which pancreatic islet beta cells are destroyed by a combination of immunological and inflammatory mechanisms. In particular, cytokine-induced production of nitric oxide has been shown to correlate with beta cell apoptosis and/or inhibition of insulin secretion. In the present study, we investigated whether the interleukin (IL)-1beta intracellular signal transduction pathway could be blocked by overexpression of dominant negative forms of the IL-1 receptor interacting protein MyD88. We show that overexpression of the Toll domain or the lpr mutant of MyD88 in betaTc-Tet cells decreased nuclear factor kappaB (NF-kappaB) activation upon IL-1beta and IL-1beta/interferon (IFN)-gamma stimulation. Inducible nitric oxide synthase mRNA accumulation and nitrite production, which required the simultaneous presence of IL-1beta and IFN-gamma, were also suppressed by approximately 70%, and these cells were more resistant to cytokine-induced apoptosis as compared with parental cells. The decrease in glucose-stimulated insulin secretion induced by IL-1beta and IFN-gamma was however not prevented. This was because these dysfunctions were induced by IFN-gamma alone, which decreased cellular insulin content and stimulated insulin exocytosis. These results demonstrate that IL-1beta is involved in inducible nitric oxide synthase gene expression and induction of apoptosis in mouse beta cells but does not contribute to impaired glucose-stimulated insulin secretion. Furthermore, our data show that IL-1beta cellular actions can be blocked by expression of MyD88 dominant negative proteins and, finally, that cytokine-induced beta cell secretory dysfunctions are due to the action of IFN-gamma.
Mots-clé
Adaptor Proteins, Signal Transducing, Animals, Antigens, Differentiation/genetics, Antigens, Differentiation/metabolism, Apoptosis, Cell Line, Gene Expression Regulation, Enzymologic/genetics, Gene Transfer Techniques, Genes, Dominant, Hela Cells, Humans, Insulin/secretion, Interferon-gamma/pharmacology, Interleukin-1/pharmacology, Islets of Langerhans/drug effects, Islets of Langerhans/metabolism, Lentivirus/genetics, Mice, Myeloid Differentiation Factor 88, NF-kappa B/metabolism, Nitric Oxide Synthase/genetics, Nitric Oxide Synthase Type II, Nitrites/metabolism, RNA, Messenger/genetics, Receptors, Immunologic, Signal Transduction
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2007 12:08
Dernière modification de la notice
20/08/2019 12:44
Données d'usage