title: RAGE and TLRs: relatives, friends or neighbours?
abstract: The innate immune system forms the first line of protection against infectious and non-infectious tissue injury. Cells of the innate immune system detect pathogen-associated molecular patterns or endogenous molecules released as a result of tissue injury or inflammation through various innate immune receptors, collectively termed pattern-recognition receptors. Members of the Toll-like receptor (TLR) family of pattern-recognition receptors have well established roles in the host immune response to infection, while the receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor predominantly involved in the recognition of endogenous molecules released in the context of infection, physiological stress or chronic inflammation. RAGE and TLRs share common ligands and signaling pathways, and accumulating evidence points towards their co-operative interaction in the host immune response. At present however, little is known about the mechanisms that result in TLR versus RAGE signalling or RAGE-TLR cross-talk in response to their shared ligands. Here we review what is known in relation to the physicochemical basis of ligand interactions between TLRs and RAGE, focusing on three shared ligands of these receptors: HMGB1, S100A8/A9 and LPS. Our aim is to discuss what is known about differential ligand interactions with RAGE and TLRs and to highlight important areas for further investigation so that we may better understand the role of these receptors and their relationship in host defense.
authors: Woolcock Institute of Medical Research, Sydney Medical School, The University of Sydney, NSW 2006, Australia; School of Pharmacy, The University of Technology, Sydney, NSW 2007, Australia; Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors: Zaridatul Aini
authors: ZA
authors: Ibrahim
authors: Carol L
authors: CL
authors: Armour
authors: Simon
authors: S
authors: Phipps
authors: Maria B
authors: MB
authors: Sukkar
mesh_terms: D040501:Calgranulin A / Q000276:immunology / Q000378:metabolism; D040502:Calgranulin B / Q000276:immunology / Q000378:metabolism; D024243:HMGB1 Protein / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D018448:Models, Immunological; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D024243:HMGB1 Protein; D008024:Ligands; D008070:Lipopolysaccharides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors
keywords: CpG-A; DAMP; HMGB1; High mobility group box-1 (HMGB1); LPS; Lipopolysaccharide (LPS); PAMP; PRR; Pattern-recognition receptors (PRRs); RAGE; Receptor for advanced glycation end products (RAGE); S100 proteins; TLR; Toll-like receptor; Toll-like receptors (TLRs); class A cytosine-guanine-rich; damage-associated molecular pattern; high mobility group box-1; lipopolysaccharides; pathogen-associated molecular pattern; pattern recognition receptor; receptor for advanced glycation end products