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.