A polysaccharide isolated from Pueraria lobata enhances maturation of murine dendritic cells

Abstract

Maturation of dendritic cells (DCs) is a critical factor for initiating the immune response. However, DC maturation is usually attenuated in the tumor microenvironment, which is an important immunological problem in DC-based immunotherapy against cancer. Here, we report the effect of a polysaccharide (PLP) isolated from Pueraria lobata on phenotypic and functional maturation of DCs. Phenotypic maturation was demonstrated by increased expression of CD40, CD86, and major histocompatibility complex I/II. PLP induced functional maturation of DCs, as shown by increased production of interleukin (IL)-12, IL-1β, and tumor necrosis factor-α, decreased antigen capture capacity, and enhanced allogenic T cell stimulation. In addition, PLP activated DCs generated from C3H/HeN mice with normal TLR4, but not DCs from C3H/HeJ mice with mutated TLR4, suggesting that the TLR4 is a membrane receptor of PLP. We showed that PLP increased ERK, JNK, and p38 mitogen-activated protein kinase phosphorylation, and nuclear translocation of the nuclear factor-kappaB p65 subunit, which are signaling molecules downstream of TLR4. These results indicate that PLP induced DC maturation through TLR4 signaling.