Expression of non-signaling membrane-anchored death receptors protects murine livers in different models of hepatitis. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Hepatology Année : 2006

Expression of non-signaling membrane-anchored death receptors protects murine livers in different models of hepatitis.

Résumé

Fas and tumor necrosis factor receptor 1 (TNFR1) are death receptors involved in various diseases such as hepatitis, sepsis, or graft rejection. Neutralizing antibodies to death ligands or soluble death receptors can inhibit cell death; however, they induce side effects because of their systemic actions. To specifically block death signaling to target cells, we created death domain-deficient (DeltaDD) membrane-anchored receptors, delivered to the liver by either recombinant adenovirus or hydrodynamic pressure of nonviral recombinant plasmids. In anti-Fas antibody-induced fulminant hepatitis, mice expressing recombinant Fas-decoy receptors (FasDeltaDD) in their livers were completely protected against apoptosis and survived fulminant hepatitis. In T-cell-dependent concanavalin A-induced autoimmune hepatitis, FasDeltaDD antagonist expression prevented hepatocyte damage and mouse death. Finally, TNFR1DeltaDD effectively protected mice against LPS-induced septic shock. In conclusion, such DeltaDD-decoy receptors act as dominant-negative receptors exerting local inhibition, while avoiding systemic neutralization of apoptosis ligands, and might have therapeutic potential in hepatitis.

Dates et versions

hal-00090520 , version 1 (31-08-2006)

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Paternité - Partage selon les Conditions Initiales

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Citer

D. Descamps, F. Vigant, S. Esselin, E. Connault, P. Opolon, et al.. Expression of non-signaling membrane-anchored death receptors protects murine livers in different models of hepatitis.. Hepatology, 2006, 44 (2), pp.314-7. ⟨10.1002/hep.21257⟩. ⟨hal-00090520⟩
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