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A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism
J T Cooper1, D M Stroka, C Brostjan
1Sandoz Center for Immunobiology, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
The Journal of Biological Chemistry
|July 26, 1996
Summary
The A20 gene inhibits endothelial cell activation by blocking nuclear factor kappaB (NF-kappaB) signaling. This novel function of A20 provides new insights into inflammatory responses and potential therapeutic targets.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- A20 is a zinc finger protein induced by tumor necrosis factor alpha (TNF).
- A20 is known to inhibit apoptosis and play a role in lymphoid cell maturation.
- The precise mechanism of A20 action remains largely unknown.
Purpose of the Study:
- To investigate the effect of A20 on endothelial cell activation.
- To elucidate the role of A20 in regulating inflammatory gene expression in endothelial cells.
Main Methods:
- Bovine aortic endothelial cells (BAEC) were transfected with A20 and reporter constructs.
- Reporter genes included promoters for E-selectin, IL-8, tissue factor, and IkappaBalpha.
- Nuclear factor kappaB (NF-kappaB) activity was assessed using specific reporter assays.
Main Results:
- A20 expression significantly inhibited the up-regulation of inflammatory genes induced by TNF, LPS, PMA, and H2O2.
- A20 suppressed NF-kappaB reporter activity, indicating a blockade of NF-kappaB signaling.
- The inhibitory effect of A20 was specific and did not affect NF-kappaB-independent reporters.
Conclusions:
- A20 inhibits endothelial cell activation through the blockade of NF-kappaB signaling.
- This study reveals a novel function of A20 in regulating endothelial cell responses to inflammatory stimuli.
- Understanding A20's role may offer new therapeutic strategies for inflammatory diseases.