Toll样受体4信号转导研究进展

Toll样受体（Toll-like-receptors，TLRs）是一个主要分布于炎症细胞的识别病源分子的受体超家族,其中TLR4主要识别革兰阴性细菌细胞壁成分脂多糖（lipopolysaccharide，LPS）。LPS与TLR4结合后活化髓样分化因子88 (myeloid differentiation factor 88, MyD88)依赖性和非依赖性两条信号途径；前者活化丝裂原激活的蛋白激酶（mitogen-activated protein kinase，MAPK）和核因子-κB（nuclear factor kappa B，NF-κB）信号通路，后者活化NF-κB和干扰素调节因子-3(IFN-regulated factor-3，IRF3)信号通路。通过这些信号途径TLR4诱导炎症细胞释放炎症因子介导炎症反应；同时TLR4通过活化树突状细胞促进抗原递呈，介导先天性免疫向获得性免疫的转化。此外，TLR4能诱导磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-AKT）的信号转导，LPS介导的细胞存活和增殖与TLR4活化 PI3K-AKT途径有关。

Progression of Toll-like receptor 4 signaling transduction

Toll-like receptors(TLRs), predominantly expressed on the inflammatory cells, are members of the pattern-recognition receptor superfamily to recognize the pathogen-associated molecular patterns. Among them, TLR4 is confirmed to be the receptor of lipopolysaccharide(LPS). When bound by LPS, TLR4 activates 2 signaling pathways, a myeloid differentiation factor 88(MyD88) dependent pathway activates mitogen-activated protein kinase(MAPK) and NF-κB, and a MyD88 independent pathway activates NF-κB and IFN-regulated factor-3(IRF-3). Through activating these signaling pathways, TLR4 induces the activation of inflammation cells to secret pro-inflammation cytokines to trigger the inflammation response. In addition, TLR4 can induce PI3K-AKT signaling, which contribute to the cell survival and proliferation induced by LPS.