Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
School of Pharmaceutics Science, Jiangnan University, Wuxi 214122, China.
Int J Biol Macromol. 2019 Apr 1;126:1158-1166. doi: 10.1016/j.ijbiomac.2019.01.022. Epub 2019 Jan 6.
Dictyophora indusiata polysaccharides (DIP) shows antioxidant, anti-tumor and immunostimulatory activities. However, the anti-inflammatory roles of DIP in NLRP3 inflammasome in LPS-stimulated macrophages are still not well defined. In this study, we investigated the mechanism of the anti-inflammatory activity of DIP in LPS-primed RAW264.7 macrophages. Our data showed that DIP inhibited NF-κB signal pathway via modulating TLR4 expression, phosphorylation of IκBα and nuclear translocation of NF-κB-p65 subunit. Meanwhile, DIP reduced inflammasome activation via decreasing NLRP3 expression in cytoplasmic pools, limiting self-assembly of NLRP3 inflammasome, as well as the subsequent activation of caspase-1 and the secretion of IL-1β and IL-18. For the first time, we show that the anti-inflammatory activity of DIP is mediated by inhibiting TLR4/NF-κB signal pathway and NLRP3 inflammasome activation during LPS-induced acute inflammation in RAW264.7 macrophages.
裂褶菌多糖（DIP）具有抗氧化、抗肿瘤和免疫刺激活性。然而，DIP 在 LPS 刺激的巨噬细胞中的 NLRP3 炎性体中的抗炎作用仍未得到很好的定义。在本研究中，我们研究了 DIP 在 LPS 预刺激的 RAW264.7 巨噬细胞中抗炎活性的机制。我们的数据表明，DIP 通过调节 TLR4 的表达、IκBα 的磷酸化和 NF-κB-p65 亚基的核易位来抑制 NF-κB 信号通路。同时，DIP 通过减少细胞质池中的 NLRP3 表达、限制 NLRP3 炎性体的自我组装以及随后的 caspase-1 激活和 IL-1β 和 IL-18 的分泌来减少炎性体的激活。我们首次表明，DIP 的抗炎活性是通过抑制 TLR4/NF-κB 信号通路和 NLRP3 炎性体激活来介导的，在 LPS 诱导的 RAW264.7 巨噬细胞急性炎症中。
