title: Platycodon grandiflorum polysaccharide induces dendritic cell maturation via TLR4 signaling.
abstract: 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.
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk 361-763, South Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk 361-763, South Korea.
authors.forename: Hwa Sun
authors.initials: HS
authors.lastname: Ryu
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk 361-763, South Korea.
authors.forename: Ji Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk 361-763, South Korea.
authors.forename: Hong Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, South Korea.
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, South Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Wonkwang University, Chonbuk 570-749, South Korea.
authors.forename: Sung Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk 361-763, South Korea.
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk 361-763, South Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk 361-763, South Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk 361-763, South Korea. Electronic address: shan@chungbuk.ac.kr.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D016899:Interferon-beta / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D031238:Platycodon / Q000737:chemistry*; D011134:Polysaccharides / Q000494:pharmacology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D009573:Nitrites; D011134:Polysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D016899:Interferon-beta
keywords: Dendritic cell; MAPK; NF-κB; Platycodon grandiflorum; TLR4