RAGE on the Toll Road?

作     者：Li Lin 

作者机构：Laboratory of Cardiovascular Sciences National Nathan Shock Drive Baltimore Maryland 21224 Institute on Aging 5600 USA Laboratory of Cardiovascular Sciences National Institute on Aging 5600 Nathan Shock Drive Baltimore Maryland 21224 USA 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2006年第3卷第5期

页      面：351-358页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：National Cancer Institute  NCI  (R01CA104912) 

主　　题：TLR RAGE NF-kB innate immunity inflammation noncanonical toll 

摘      要：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-kB, 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-kB, 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. Cellular ＆ Molecular Immunology.