NERVOUS REGULATION · Cholinergic control of macrophage activation and functions
6РП — Действия „Мария Кюри“
- Период
- 2006-10-23 → 2008-09-22
- Финансиране от ЕС
- 227 626 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Връзката между нервната и имунната система се проучва чрез влиянието на холинергичните рецептори върху макрофагите. Това помага да се разбере как определени невротрансмитери намаляват възпалителните реакции и променят начина, по който имунните клетки реагират на патогени.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - NERVOUS REGULATION (Cholinergic control of macrophage activation and functions)
Focus of the research was to investigate functional links of the nervous and immune systems, especially on innate immune cells. A general screening of neurotransmitter receptor systems on macrophages from several body compartments is achieved. Initial focus has been the class of cholinergic receptors. At a cellular level it is found that cholinergic agonists generally negatively influence the immune response to pathogens. I have shown that cholinergic agonists induce a tolerant phenotype in innate immune cells, and increase microbe and particle uptake, whilst reducing inflammatory responses. Expression profiling in mouse and human macrophages has indicated that cholinergic receptor expression varies amongst species. Furthermore, a technical achievement is the generation of several reporter cells systems that allow high throughput study for neurotransmitters that interfere with activation of the NF-kB pathway.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Brain activity can modulate immune responses, but mechanisms involved have remained an enigma. Here, we will substantiate modulation of the innate immune response by the parasympathetic nervous system and evaluate the receptors and signal transduction mechanisms involved.Excessive inflammation is devastating to tissue and counter-regulatory systems are needed to keep immune responses under control. In a mouse model of intestinal inflammation, we have recently demonstrated that such a mechanism is provided by the cholinergic nervous system. Our data, and that of others, suggest that particularly the vagal nerve, the largest nerve of the body, can reflexively monitor and regulate activation of enteric macrophages (the main class of innate immune cells) via peripheral release of its neurotransmitter acetylcholine. Compared to the classically known regulation of macrophage activation via humoral pathways (i.e. cytokines), neuronal signalling can be rapid, targeted, and directly integrated. This concept is supported by in vivo as well as in vitro data, as acetylcholine negatively regulates macrophage activation via acetylcholine receptors present on these cells.In the current project we will study which receptors for acetylcholine are involved in the cholinergic nervous systems control of macrophage activation. Cellular responses of macrophages to acetylcholine, and the receptor involved will be determined. We will study which macrophage populations express the acetylcholine receptor, and how these cells respond to agonists of this receptor.Several acetylcholine receptor agonists are now used to treat neurological disorders. The efficacy of these compounds to regulate inflammatory signalling will be addressed. Also, their efficacy to ameliorate inflammatory disease will be studied in models of enteric inflammation to explore their potential as novel class of anti-inflammatory drugs.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OXFORDКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз