Platycodon grandiflorum polysaccharide induces dendritic cell maturation via TLR4 signaling

• Published in: Food and chemical toxicology Vol. 72; pp. 212 - 220
• Main Authors: MI JEONG PARK, HWA SUN RYU, HAN, Sang-Bae, JI SUNG KIM, HONG KYUNG LEE, JONG SOON KANG, JIEUN YUN, SUNG YEON KIM, MI KYEONG LEE, JIN TAE HONG, YOUNGSOO KIM
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01.10.2014
• Subjects: Animals; Biological and medical sciences; Cell Differentiation - drug effects; Cell Line; Cell Proliferation - drug effects; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Endocytosis - drug effects; Female; Food toxicology; Interferon-beta - metabolism; Interleukin-10 - metabolism; Interleukin-12 - metabolism; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; NF-kappa B - metabolism; Nitrites - metabolism; Phosphorylation - drug effects; Platycodon - chemistry; Platycodon grandiflorum; Polysaccharides - pharmacology; Signal Transduction; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toxicology; Tumor Necrosis Factor-alpha - metabolism; Dendritic cell; Enzyme; Transferases; Mitogen-activated protein kinase; MAPK; Platycodon grandiflorum; Signal transduction; NF-κB; Dicotyledones; Angiospermae; Campanulaceae; Spermatophyta; Transcription factor NFκB; Polysaccharide; TLR4
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2014.07.011

Dendritic cell (DC) maturation is critical for initiation of the adoptive immune response. DC maturation is often attenuated in several pathological conditions including cancer. In this study, we report the effect of Platycodon grandiflorum polysaccharide (PG) on DC maturation. PG induced phenotypic maturation of DCs, as proved by the increase in the expression of CD40, CD80, CD86, and major histocompatibility complex (MHC)-I/II on the cell surface. PG also induced functional maturation of DCs, as proved by elevated production of interleukin (IL)-12, tumor necrosis factor-α, IL-1β, IL-6, IL-10, and interferon-β, and by enhanced allogeneic T cell stimulation ability of PG-treated DCs. PG efficiently induced maturation of DCs from C3H/HeN mice, which have normal Toll-like receptor-4 (TLR4), but not that of DCs from C3H/HeJ mice, which have mutated TLR4, suggesting that TLR4 might be one of the PG receptors in DCs. In line with TLR4 activation, PG increased the phosphorylation of ERK, p38, and JNK, and the nuclear translocation of p-c-Jun, p-CREB, and c-Fos. PG also activated NF-κB signaling, as evidenced by degradation of IκBα/β and nuclear translocation of p65 and p50. In summary, our data suggest that PG induces DC maturation by activating MAPK and NF-κB signaling downstream of TLR4.