RAGE: A new frontier in chronic airways disease

Sukkar, MB; Ullah, MA; Gan, WJ; Wark, PAB; Chung, KF; Hughes, JM; Armour, CL; Phipps, S

RAGE: A new frontier in chronic airways disease

Sukkar, MB

Ullah, MA Gan, WJ Wark, PAB Chung, KF Hughes, JM Armour, CL Phipps, S

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Publication Type:: Journal Article
Citation:: British Journal of Pharmacology, 2012, 167 (6), pp. 1161 - 1176
Issue Date:: 2012-11-01

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Field	Value	Language
dc.contributor.author	Sukkar, MB https://orcid.org/0000-0003-4591-2399	en_US
dc.contributor.author	Ullah, MA	en_US
dc.contributor.author	Gan, WJ	en_US
dc.contributor.author	Wark, PAB	en_US
dc.contributor.author	Chung, KF	en_US
dc.contributor.author	Hughes, JM	en_US
dc.contributor.author	Armour, CL	en_US
dc.contributor.author	Phipps, S	en_US
dc.date.issued	2012-11-01	en_US
dc.identifier.citation	British Journal of Pharmacology, 2012, 167 (6), pp. 1161 - 1176	en_US
dc.identifier.issn	0007-1188	en_US
dc.identifier.uri	http://hdl.handle.net/10453/23188
dc.description.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. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.	en_US
dc.relation.ispartof	British Journal of Pharmacology	en_US
dc.relation.isbasedon	10.1111/j.1476-5381.2012.01984.x	en_US
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive	en_US
dc.subject.mesh	Receptors, Immunologic	en_US
dc.subject.mesh	Ligands	en_US
dc.subject.mesh	Advanced Glycosylation End Product-Specific Receptor	en_US
dc.subject.mesh	Receptor for Advanced Glycation End Products	en_US
dc.title	RAGE: A new frontier in chronic airways disease	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.citation.volume	167	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
utslib.copyright.status	closed_access
pubs.issue	6	en_US
pubs.publication-status	Published	en_US
pubs.volume	167	en_US

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. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

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http://hdl.handle.net/10453/23188