title: Promoting effect of polysaccharide isolated from Mori fructus on dendritic cell maturation.
abstract: Maturation of dendritic cells (DCs) is usually attenuated in the tumor microenvironment, which is an important immunological problem in DC-based immunotherapy of cancer. In this study, we report the effect of a Mori fructus polysaccharide (MFP) on DC maturation. MFP was treated to DCs generated from mouse BM cells. MFP induced phenotypic maturation of DCs, as proven by the increased expression of CD40, CD80/86, and MHC-I/II molecules. MFP induced functional maturation of DCs, in that MFP increased the expression of IL-12, IL-1β, TNF-α, and IFN-β, decreased antigen capture capacity, and enhanced allogenic T cell stimulation. MFP efficiently induced maturation of DCs from C3H/HeN mice having normal toll-like receptor4 (TLR4), but not DCs from C3H/HeJ mice having mutated TLR4, suggesting that TLR4 might be one of the membrane receptors of MFP. As a mechanism of action, MFP increased phosphorylation of mitogen-activated protein kinase (MAPKs), and nuclear translocation of NF-κB p65 subunit, which were important signal molecules downstream from TLR4. These data suggest that MFP induces DC maturation through TLR4 and MFP can be used as an adjuvant in DC-based cancer immunotherapy.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Shin
authors.forename: Hyung Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Yun
authors.forename: Hong Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Yeon Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Sung Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Lee
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D031625:Morus / Q000737:chemistry*; D010766:Phosphorylation / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D011134:Polysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4