supernatant from bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells上层清液从双歧杆菌不同调节转导信号通路对人类树突细胞的生物功能.pdf

Supernatant from Bifidobacterium Differentially Modulates Transduction Signaling Pathways for Biological Functions of Human Dendritic Cells 1 1 1 1 1 ´ Cyrille Hoarau *, Laurence Martin , Delphine Faugaret , Christophe Baron , Audrey Dauba , Cecile Aubert-Jacquin2, Florence Velge-Roussel1,3, Yvon Lebranchu1 ´ ´ ´ ´ 1 UPRES EA 4245 « Cellules Dendritiques Greffes », Universite Franc¸ois-Rabelais, Tours, France, 2 Departement de Recherche et Developpement Bledina, Villefranche sur ˆ ´ Saone, France, 3 UFR des Sciences Pharmaceutiques, Universite Franc¸ois-Rabelais, Tours, France Abstract Background: Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, the signaling pathways engaged by probiotics are poorly understood. We have previously reported that a fermentation product from Bifidobacterium breve C50 (BbC50sn) could induce maturation, high IL-10 production and prolonged survival of DCs via a TLR2 pathway. We therefore studied the roles of mitogen- activated protein kinases (MAPK), glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K) pathways on biological functions of human monocyte-derived DCs treated with BbC50sn. Methodology/Principal Findings: DCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50sn, lipopolysaccharide (LPS) or Zymosan, with or without specific inhibitors of p38MAPK (SB203580), ERK (PD98059), PI3K (LY294002) and GSK3 (SB216763). We found that 1) the PI3K pathway w