地塞米松对脂多糖激活的核因子-κB信号通路作用机制研究进展

Advances in Mechanisms of Effect of Dexamethasone on Lipopolysaccharide-Activated NF-κB Signaling Pathway

脂多糖(LPS)是重要的炎症诱导因子,可通过与炎症相关细胞膜表面的Toll样受体4(TLR4)结合入胞并激活下游信号通路,促使核因子(NF)-κB进行核转位从而启动目标基因的转录,合成促炎因子推动炎症反应的进行。地塞米松作为强效的糖皮质激素可通过一系列“基因组效应”调控LPS-TLR4/NF-κB信号通路中的多个组分,影响炎症因子的合成,改变炎症转归。文章综述了LPS通过TLR4激活NF-κB通路的机制以及地塞米松对LPS-TLR4/NF-κB通路的作用机制相关研究进展,并列举了影响地塞米松对该通路作用的因素。该方面研究的深入可能有望指导地塞米松临床应用的安全剂量范围并为脓毒症等疾病提供新的治疗思路。

Lipopolysaccharide(LPS),an important inflammatory inducer,binds to Toll-like receptor 4(TLR4)on the surface of inflammation-related cell membrane and activates downstream signaling pathway.The nuclear translocation of NF-κB initiates transcription procedure of the target genes,synthesizing pro-inflammatory factors to promote the inflammatory response.As a potent glucocorticoid,dexamethasone can regulate multiple components in the LPS/TLR4/NF-κB signaling pathway through a series of‘genomic effects’,affecting the synthesis of inflammatory factors and altering inflammatory outcome.This article reviews TLR4-mediated mechanisms of LPS-activated NF-κB pathway,as well as the effect of dexamethasone on LPS/TLR4/NF-κB pathway and its influencing factors.Further research in this area may guide the safe dosage range for clinical use of dexamethasone and provide new therapeutic approaches for diseases such as sepsis.