Periodic Report Summary - A20APOPTOSIS (Molecular and structural analysis of A20 in the modulation of apoptosis: anti-inflammatory potential in vasculitis)
The activated neutrophils play a deleterious role in vasculitis lesions as suggested by their presence in perivascular infiltrates and especially in kidney glomeruli and in the lung. Because NF-kB activation in response to tumour necrosis factor TNF-alpha has been described as a main pathway in neutrophil survival, it can be foreseen that A20, a powerful inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), will play a role in the regulation of neutrophil apoptosis and thus in the regulation of the inflammation.
Summary description of the project objectives
We proposed to analyse the respective role of A20, a 90kDa zinc finger protein that serves an essential role in the termination of TNF-alpha and LPS-mediated NF-kB pathway, in both endothelial cells and neutrophils, two cardinal cell players in inflammation associated vasculitis.
Preliminary data obtained in the laboratory have clearly shown that A20 protein can be detected in inflammatory neutrophils. However, the precise role of A20 is not known. Because A20 can have either an anti-or a pro-apoptotic role, investigation on the effect of A20 expression on neutrophil apoptosis is a key issue and had to be carried out.
Description of the work performed
During this first year, we focused our effort on the investigation of A20 activity in neutrophils. In contrast to endothelial cells, neutrophils have never been investigated for their capacities to express A20 and whether A20, if expressed could modulate their apoptosis.
Summary description of the project objectives
We proposed to analyse the respective role of A20, a 90kDa zinc finger protein that serves an essential role in the termination of TNF-alpha and LPS-mediated NF-kB pathway, in both endothelial cells and neutrophils, two cardinal cell players in inflammation associated vasculitis.
Preliminary data obtained in the laboratory have clearly shown that A20 protein can be detected in inflammatory neutrophils. However, the precise role of A20 is not known. Because A20 can have either an anti-or a pro-apoptotic role, investigation on the effect of A20 expression on neutrophil apoptosis is a key issue and had to be carried out.
Description of the work performed
During this first year, we focused our effort on the investigation of A20 activity in neutrophils. In contrast to endothelial cells, neutrophils have never been investigated for their capacities to express A20 and whether A20, if expressed could modulate their apoptosis.