RAGE: a new frontier in chronic airways disease.

School of Pharmacy, The University of Technology Sydney, NSW, Australia Woolcock Institute of Medical Research, Sydney Medical School, The University of Sydney, NSW, Australia School of Biomedical Sciences and Australian Infectious Diseases Research Centre, The University of Queensland, Qld, Australia Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, NSW, Australia Department of Respiratory and Sleep Medicine, John Hunter Hospital, NSW, Australia Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK Faculty of Pharmacy, The University of Sydney, NSW, Australia.
British Journal of Pharmacology (Impact Factor: 5.07). 04/2012; 167(6):1161-1176. DOI: 10.1111/j.1476-5381.2012.01984.x
Source: PubMed

ABSTRACT Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand-RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.

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May 27, 2014