RAGE on the Toll Road?
RAGE on the Toll Road?
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DOI：
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发表时间：
2006-10
影响因子：
24.1
通讯作者：
Li Lin
中科院分区：
文献类型：
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作者：
Li Lin
哺乳动物 Toll 样受体 (TLR) 是细胞模式识别受体 (PRR)，可识别病原体的分子模式。在与致病性模式配体结合后，单核细胞和巨噬细胞中 TLR 的胞质部分通过受体驱动的信号级联募集接头蛋白，激活转录因子 NF-κB，导致促炎细胞因子的表达，从而引发炎症。这种快速的先天细胞反应是宿主抵御病原体感染的第一道防线，也刺激适应性免疫系统清除入侵的微生物。越来越多的证据表明，TLR 还识别宿主衍生的配体，将这组 PRR 与可能没有与感染直接相关的病因学的疾病联系起来。晚期糖基化终产物（AGE）是在氧化应激和高血糖环境中形成的非酶糖化或氧化的蛋白质、脂质和核酸。 AGE 与其受体 RAGE 结合会启动激活 NF-kappaB 的细胞信号，从而导致促炎因子的转录。 RAGE 还可以与细胞死亡和组织损伤产生的其他内源配体相互作用。 RAGE 与糖尿病、动脉粥样硬化、神经疾病、癌症以及衰老等慢性疾病有关。这篇综述讨论了 RAGE 作为 PRR 的可能作用，它可能使用与 TLR 平行的信号机制来引发炎症反应。因此，在这种情况下，RAGE 可能在复杂疾病进展背景下的细胞稳态调节中发挥重要作用。
Mammalian Toll-like receptors (TLRs) are cellular pattern-recognizing receptors (PRRs) that recognize the molecular patterns of pathogens. After engaging the pathogenic patterned ligands, the cytosolic portion of the TLRs in monocytes and macrophages, recruits adaptor proteins, via a receptor-driven signaling cascade, activates the transcription factor NF-kappaB, leading to the expression of proinflammatory cytokines, which trigger inflammation. Such rapid, innate cellular responses serve as the first line of host defense against infection by pathogens, and also stimulate the adaptive immune system to clear the invading microbes. Increasing evidence suggests that TLRs also recognize host-derived ligands, linking this group of PRRs to diseases that may not have an etiology that is associated directly with infections. Advanced glycation end products (AGEs) are nonenzymatically glycated or oxidated proteins, lipids and nucleic acids that are formed in the environment of oxidant stress and hyperglycemia. Binding of AGEs to their receptor RAGE initiates cellular signals that activate NF-kappaB, which results in transcription of proinflammatory factors. RAGE can also interact with other endogenous ligands generated by cell death and tissue injuries. RAGE has been implicated in chronic diseases such as diabetes, atherosclerosis, neurodisorders, cancers, as well as aging. This review discusses the possible role of RAGE as a PRR that may use signaling mechanisms parallel to TLRs', to solicit inflammatory reactions. Thus, in this scenario, RAGE may play a prominent role in the regulation of cellular homeostasis in the context of complex disease progression.