MAPK/ERK通路
TLR4型
磷酸化
p38丝裂原活化蛋白激酶
NF-κB
Toll样受体
信号转导
细胞生物学
αBκ
化学
肿瘤坏死因子α
受体
脂多糖
污渍
激酶
促炎细胞因子
NFKB1型
炎症
分子生物学
生物
免疫学
生物化学
先天免疫系统
转录因子
基因
作者
Changkai Zhou,Jing Gao,Hongyan Ji,Wenjing Li,Xiaoyan Xing,Donghua Liu,Qie Guo,Ling Zhou,Fanbo Jing
出处
期刊:Inflammation
[Springer Nature]
日期:2021-07-16
卷期号:44 (5): 2018-2032
被引量:11
标识
DOI:10.1007/s10753-021-01478-z
摘要
Previous studies have shown that benzoylaconine (BAC), a representative monoester alkaloid, has a potential anti-inflammatory effect. This study investigated the underlying molecular mechanisms using the mode of LPS-activated RAW264.7 macrophage cells. Our findings showed that BAC significantly suppressed the release of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, IL-1β, ROS, NO, and PGE2. BAC treatment also effectively downregulated the elevated protein levels of iNOS and COX-2 induced by LPS in a dose-dependent manner. In this study, we found that BAC inhibited LPS-induced NF-κB activation by reducing the phosphorylation and degradation of IκBα by western blotting and blocking the nuclear translocation of p65 using an immunofluorescence assay. The elevated protein levels of JNK, p38, and ERK phosphorylation after LPS stimulation were restored effectively by BAC treatment. The protein expression of Toll-like receptor 4 (TLR4) and LPS-induced phosphorylation of TAK1, which is a crucial upstream regulatory factor of TLR-induced MAPK and NF-κB signaling, were inhibited by BAC in activated RAW264.7 macrophages. Moreover, BAC decreased the levels of TAK1 phosphorylation and pro-inflammatory cytokines and mediators associated with MAPK and NF-κB activation, similar to TLR4 inhibitor TAK-242. These findings demonstrated that BAC exhibited an anti-inflammatory effect by the inhibition of TLR-induced MAPK and NF-κB pathways, indicating that it could potentially be used for treating inflammatory diseases.
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