title: The role of receptor for advanced glycation end products in airway inflammation in CF and CF related diabetes.
abstract: Cystic Fibrosis (CF) is often accompanied by diabetes leading to worsening lung function, the reason for which is unclear. The receptor for advanced-glycation-end-products (RAGE) regulates immune responses and inflammation and has been linked to diabetes and possibly CF. We performed a pilot study to determine if CF and CF-related diabetes (CFRD) are associated with enhanced RAGE expression. Full length (fl)RAGE, soluble (s)RAGE, endogenous soluble (es)RAGE, S100A12 (enRAGE) and advanced-glycation-end-products (AGE) expression was assessed in serum, white blood cells and sputum of patients with CF; diabetes; CFRD and healthy subjects. Sputum enRAGE/sRAGE ratios were high in CF but particularly in CFRD which negatively correlated with % predicted FEV1. Serum AGE and AGE/sRAGE ratios were high in diabetics but not in CF. A complex, multifaceted approach was used to assess the role of RAGE and its ligands which is fundamental to determining their impact on airway inflammation. There is a clear association between RAGE activity in the airways of CF and CFRD patients that is not evident in the vascular compartment and correlates with lung function, in contrast to diabetes. This strongly suggests a role for RAGE in contributing to the inflammatory overdrive seen in CF and to a greater extent in CFRD.
authors.affiliation: 1] Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia [2] Lung Institute of Western Australia, Nedlands, Western Australia [3] Centre for Asthma, Allergy and Respiratory Research, School of Medicine and Pharmacology, University of Western Australia, Western Australia.
authors.forename: Siobhain
authors.initials: S
authors.lastname: Mulrennan
authors.affiliation: 1] Lung Institute of Western Australia, Nedlands, Western Australia [2] Centre for Asthma, Allergy and Respiratory Research, School of Medicine and Pharmacology, University of Western Australia, Western Australia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Baltic
authors.affiliation: 1] Lung Institute of Western Australia, Nedlands, Western Australia [2] Centre for Asthma, Allergy and Respiratory Research, School of Medicine and Pharmacology, University of Western Australia, Western Australia.
authors.forename: Shashi
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: 1] Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia [2] Lung Institute of Western Australia, Nedlands, Western Australia.
authors.forename: Jamie
authors.initials: J
authors.lastname: Wood
authors.affiliation: PathWest, Sir Charles Gairdner Hospital, Nedlands, Western Australia.
authors.forename: Alina
authors.initials: A
authors.lastname: Miranda
authors.affiliation: PathWest, Sir Charles Gairdner Hospital, Nedlands, Western Australia.
authors.forename: Felicity
authors.initials: F
authors.lastname: Frost
authors.affiliation: Department of Endocrinology, Sir Charles Gairdner Hospital, Nedlands, Western Australia.
authors.forename: Joey
authors.initials: J
authors.lastname: Kaye
authors.affiliation: 1] Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia [2] Lung Institute of Western Australia, Nedlands, Western Australia [3] Centre for Asthma, Allergy and Respiratory Research, School of Medicine and Pharmacology, University of Western Australia, Western Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003920:Diabetes Mellitus / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000097:blood / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products / Q000096:biosynthesis* / Q000097:blood; D013183:Sputum / Q000378:metabolism
chemical_list: C000593871:AGER protein, human; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products