Park Mi Jeong, Ryu Hwa Sun, Kim Ji Sung, Lee Hong Kyung, Kang Jong Soon, Yun Jieun, Kim Sung Yeon, Lee Mi Kyeong, Hong Jin Tae, Kim Youngsoo, Han Sang-Bae
College of Pharmacy, Chungbuk National University, Chungbuk 361-763, South Korea.
Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, South Korea.
Food Chem Toxicol. 2014 Oct;72:212-20. doi: 10.1016/j.fct.2014.07.011. Epub 2014 Jul 11.
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.
树突状细胞（DC）成熟对于启动过继性免疫反应至关重要。在包括癌症在内的多种病理状况下，DC成熟常常会减弱。在本研究中，我们报告了桔梗多糖（PG）对DC成熟的影响。PG诱导DC发生表型成熟，细胞表面CD40、CD80、CD86以及主要组织相容性复合体（MHC）-I/II表达增加即证明了这一点。PG还诱导DC发生功能成熟，PG处理的DC产生白细胞介素（IL）-12、肿瘤坏死因子-α、IL-1β、IL-6、IL-10和干扰素-β增加，以及异体T细胞刺激能力增强即证明了这一点。PG能有效诱导具有正常Toll样受体4（TLR4）的C3H/HeN小鼠的DC成熟，但不能诱导具有突变TLR4的C3H/HeJ小鼠的DC成熟，这表明TLR4可能是DC中PG的受体之一。与TLR4激活一致，PG增加了ERK、p38和JNK的磷酸化以及p-c-Jun、p-CREB和c-Fos的核转位。PG还激活了NF-κB信号通路，IκBα/β降解以及p65和p50核转位证明了这一点。总之，我们的数据表明PG通过激活TLR4下游的MAPK和NF-κB信号通路诱导DC成熟。
