TLR4型
促炎细胞因子
炎症体
药理学
信号转导
活力测定
细胞因子
炎症
免疫学
免疫系统
生物
医学
微生物学
细胞凋亡
生物化学
作者
Fei Jiang,Jiebang Jiang,Wenping He,Guokai Dong,Nana Xu,Li Meng,Yunyun Zhao,Meng Wang,Shirui Tan,Yongping Shi,Rongpeng Li
摘要
Abstract Acute lung injury (ALI) caused by acute bacterial infection remains a common life‐threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L. , has various biological functions, including anti‐inflammatory, anti‐cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)‐induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP‐infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll‐like receptor 4/nuclear factor kappa‐B (TLR4/NF‐κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF‐κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c‐Jun N‐terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD‐like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr‐alleviated ALI via inhibiting pro‐inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP‐induced ALI.
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