A20APOPTOSIS · Molecular and structural analysis of A20 in the modulation of apoptosis: anti-inflammatory potential in vasculitis
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2008-04-01 → 2012-03-31
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-IRG
Линиите свързват координатора с партньорите.
Накратко на български
Протеинът A20 и неговата роля при програмираната смърт на неутрофилните клетки се анализират при васкулит. Това помага да се разбере как се регулира възпалението в кръвоносните съдове, белите дробове и бъбреците.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
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.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The ubiquitin editing protein A20, a novel 90kDa zinc-finger protein has an universal anti-inflammatory activity by inhibiting NF-kappaB activation. In endothelial cells, the induction of A20 by inflammatory stimuli renders cells resistant to apoptosis. However, A20 can have pro-apoptotic activities in other cell types. We will focus on the respective role of A20 in both endothelial cells and neutrophils, two cardinal cell players in inflammation associated with autoimmune vasculitis in which A20 could be a suitable therapeutic target and has never been investigated. We hypothesized that this differential effect of A20 in modulating apoptosis and inflammation is dependent on different molecular partner A20. Hence, we proposeto i) identify the A20 interactome by proteomic and modelisation approaches in both endothelial cells and neutrophils, ii) investigate the function of A20 in neutrophils, iii) study A20 modulation of neutrophil-mediated endothelial cell toxicity, iii) investigate A20 expression in patients with vasculitis. Through its interdisciplinary and integrative approaches combining molecular biology, cell biology, functional biology, molecular modeling and clinical investigations, this project directed by Dr Daniel, an expert of A20, constitutes a timely and novative approach to unravel the role of A20 and A20-binding proteins in modulating apoptosis and inflammation and identify novel therapeutic tools.
Оригинален текст от CORDIS (на английски).
Участници
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisКоординаторФранция
Връзки
Данни: CORDIS, © Европейски съюз