Details

Autor(en) / Beteiligte

• Ferran, Christiane
• Stroka, Deborah M.
• Badrichani, Anne Z.
• Cooper, Jeffrey T.
• Wrighton, Christopher J.
• Soares, Miguel
• Grey, Shane T.
• Bach, Fritz H.

Titel

A20 Inhibits NF-κB Activation in Endothelial Cells Without Sensitizing to Tumor Necrosis Factor–Mediated Apoptosis

Ist Teil von

• Blood, 1998-04, Vol.91 (7), p.2249-2258

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

1998

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Expression of the NF-κB–dependent gene A20 in endothelial cells (EC) inhibits tumor necrosis factor (TNF)–mediated apoptosis in the presence of cycloheximide and acts upstream of IκBα degradation to block activation of NF-κB. Although inhibition of NF-κB by IκBα renders cells susceptible to TNF-induced apoptosis, we show that when A20 and IκBα are coexpressed, the effect of A20 predominates in that EC are rescued from TNF-mediated apoptosis. These findings place A20 in the category of “protective” genes that are induced in response to inflammatory stimuli to protect EC from unfettered activation and from undergoing apoptosis even when NF-κB is blocked. From a therapeutic perspective, genetic engineering of EC to express an NF-κB inhibitor such as A20 offers the mean of achieving an anti-inflammatory effect without sensitizing the cells to TNF-mediated apoptosis.