TNF-α and IFN-γ are potential inducers of Fas-mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis.

Détails

ID Serval
serval:BIB_B02933AADC86
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TNF-α and IFN-γ are potential inducers of Fas-mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis.
Périodique
The Journal of investigative dermatology
Auteur⸱e⸱s
Viard-Leveugle I., Gaide O., Jankovic D., Feldmeyer L., Kerl K., Pickard C., Roques S., Friedmann P.S., Contassot E., French L.E.
ISSN
1523-1747 (Electronic)
ISSN-L
0022-202X
Statut éditorial
Publié
Date de publication
02/2013
Peer-reviewed
Oui
Volume
133
Numéro
2
Pages
489-498
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Toxic epidermal necrolysis (TEN) is a severe immune-mediated adverse cutaneous drug eruption characterized by rapid and extensive epithelial cell death in the epidermis and mucosae. The molecular events leading to this often fatal condition are only partially understood, but evidence suggests a dual mechanism implicating a "drug"-specific immune response on one side and the onset of target cell death by proapoptotic molecules including FasL on the other side. Herein, we describe a potential molecular bridge between these two events that involves inducible nitric oxide synthase (iNOS), which is highly upregulated in the skin of TEN patients. We show that activated T cells secrete high amounts of tumor necrosis factor-α (TNF-α) and IFN-γ, and that both cytokines lead to increased expression and activity of keratinocyte iNOS. A similar observation has been made with drug-specific T lymphocytes from a TEN patient exposed to the culprit drug. The resulting increase in nitric oxide significantly upregulates keratinocyte FasL expression, resulting in Fas- and caspase-8-mediated keratinocyte cell death. Taken together, our data suggest that T-lymphocyte activation by drugs in TEN patients may indirectly lead to FasL-mediated keratinocyte apoptosis, via a molecular bridge involving TNF-α, IFN-γ, and iNOS.

Mots-clé
Antigens, CD95/immunology, Antigens, CD95/metabolism, Apoptosis/immunology, Caspase 8/immunology, Caspase 8/metabolism, Cell Line, Drug Synergism, Fas Ligand Protein/genetics, Fas Ligand Protein/immunology, Fas Ligand Protein/metabolism, Foreskin/cytology, Humans, Interferon-gamma/immunology, Interferon-gamma/metabolism, Interferon-gamma/pharmacology, Keratinocytes/cytology, Keratinocytes/drug effects, Keratinocytes/metabolism, Male, Nitric Oxide/metabolism, Nitric Oxide Donors/pharmacology, Nitric Oxide Synthase Type II/genetics, Nitric Oxide Synthase Type II/immunology, Nitric Oxide Synthase Type II/metabolism, Oxidative Stress/drug effects, Oxidative Stress/immunology, Primary Cell Culture, RNA, Messenger/metabolism, Stevens-Johnson Syndrome/immunology, Stevens-Johnson Syndrome/metabolism, Stevens-Johnson Syndrome/pathology, T-Lymphocytes/cytology, T-Lymphocytes/immunology, T-Lymphocytes/metabolism, Tumor Necrosis Factor-alpha/immunology, Tumor Necrosis Factor-alpha/metabolism, Tumor Necrosis Factor-alpha/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/11/2017 10:57
Dernière modification de la notice
20/08/2019 15:19
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