. Tout-d-'abord-dans-les-raw264, 7, nous avons pu mettre en évidence une absence de cytotoxicité de l'extrait polyphénolique de vin sur ces cellules (Figure 18) Puis nous avons confirmé que le LPS induit le « priming » des macrophages (Figure 19), 2015.

. Shen, Nous avons ensuite voulu savoir si l'extrait de vin agit sur le « priming » de NLRP3 ou sur l'activation et la formation de l'inflammasome, 2016.

. Lin, Ces résultats contradictoires s'accordent avec les grandes variations de résultats observées dans la littérature En effet ces cellules sont décrites par certains comme ayant une déficience pour l'expression de la protéine ASC Or ASC est la protéine adaptatrice qui permet la liaison avec ses partenaires NLRP3 et la caspase-1 et ainsi la formation de l'inflammasome, ASC est donc indispensable pour le clivage de la, 2008.

. Lin, capspase-1 et de la pro-IL-1? en caspase-1 active et IL-1? mature, 2004.

. Nous-avons-alors-montré-que-les-raw264, 7 présentent un faible taux d'expression d'ASC à la fois par PCR et par Western Blot (Figure 23, 27 et 28) ; néanmoins nous arrivons à détecter son expression par immunofluorescence

. Par-ailleurs-dans-la-bibliographie and . Verhoef, ont mis en évidence un défaut au niveau des voies de signalisations liées au récepteur purinergique P2X7 nécessaire à la formation de l'inflammasome et au clivage de la caspase-1 dans les Raw264

. De-plus and . Antonopoulos, ont pu mettre en évidence une suppression complète de la production d'IL-1? par des macrophages issus de moelle osseuse de souris déficientes pour ASC (Antonopoulos, 2013.

. Xiang, 7 par du LPS est un modèle idéal pour l'étude de l'inflammation via la voie canonique Xiao et coll. ont révélé une augmentation de l'expression des composants de l'inflammasome NLRP3 dans les cellules RAW 264.7 après traitement par LPS. Cependant, cette augmentation de NLRP3 et la production d'IL-1? peut être inhibée par un prétraitement à l'Orientine D'autres auteurs, montrent qu'une molécule nommée NZ est capable de diminuer la production d'IL-1? et d'IL-18, Or d'autres publications indiquent que le traitement des cellules Raw264, 2015.

. Dans-le-cadre-de-notre-Étude, expression protéique et génique de NLRP3 dans les Raw264.7 « primés » et activés et prétraités par l'extrait de vin, nous suggérons que l'extrait polyphénolique de vin rouge n'a pas d'action sur le « priming » de l'inflammasome NLRP3. Qu'en est-il de son effet sur l'activation et l'assemblage de l'inflammasome NLRP3 ?

. Parallèlement, immunomarquage nous montre une diminution de la colocalisation NLRP3/ASC en présence d'un traitement par l'extrait de vin après priming et avant activation

«. Concernant-le and N. De, nous observons, sur les macrophages J774A.1 prétraités par l'extrait de vin, « primés » et activés, une diminution de l'expression protéique de NLRP3 et ASC mais également une diminution de la production d'IL-1? mature

. Cependant, la première partie de l'analyse nous indique que l'extrait de vin a un effet sur le « priming » de l'inflammasome NLRP3

N. De-plus-il-serait-intéressant-de and . Mapk-dans-les-macrophages, En effet, il a été montré que ces voies de signalisation sont impliquées dans l'expression de l'IL-1? Dans ce contexte, Lee et coll. ont montré un effet suppresseur de l'inflammasome NLRP3 de la sinigrine et in fine une diminution de la production d'IL-1?, pp.3-4, 2009.

. Nous-avons-mis-en-Évidence and . Au-travers-de-cette-Étude, que l'extrait polyphénolique de vin rouge se dévoile comme un candidat intéressant de par son activité immunomodulatrice antiinflammatoire . En effet, il présente des effets inhibiteurs sur la production de cytokines pro inflammatoires aussi bien sur la réponse immunitaire innée que sur la réponse immunitaire adaptative. L'extrait polyphénolique de vin rouge pourrait donc être un axe nutritionnel important dans la prévention de l

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