The Role of Receptor for Advanced Glycation End Products in Airway Inflammation in CF and CF related Diabetes

被引:39
作者
Mulrennan, Siobhain [1 ,2 ,3 ]
Baltic, Svetlana [2 ,3 ]
Aggarwal, Shashi [2 ,3 ]
Wood, Jamie [1 ,2 ]
Miranda, Alina [4 ]
Frost, Felicity [4 ]
Kaye, Joey [5 ]
Thompson, Philip J. [1 ,2 ,3 ]
机构
[1] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia
[2] Lung Inst Western Australia, Nedlands, WA, Australia
[3] Univ Western Australia, Sch Med & Pharmacol, Ctr Asthma Allergy & Resp Res, Nedlands, WA 6009, Australia
[4] Sir Charles Gairdner Hosp, PathWest, Nedlands, WA 6009, Australia
[5] Sir Charles Gairdner Hosp, Dept Endocrinol, Nedlands, WA 6009, Australia
来源
SCIENTIFIC REPORTS | 2015年 / 5卷
关键词
SOLUBLE RECEPTOR; CYSTIC-FIBROSIS; RAGE; NEURODEGENERATION; COMPLICATIONS; ENDPRODUCTS; EXPRESSION; LIGANDS;
D O I
10.1038/srep08931
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:9
相关论文
共 20 条
[1]   Serum soluble receptor for advanced glycation end products (sRAGE) is independently associated with cigarette smoking in non-diabetic healthy subjects [J].
Biswas, Subrata K. ;
Mudi, Sonchita R. ;
Mollah, Forhadul H. ;
Bierhaus, Angelika ;
Arslan, M. Iqbal .
DIABETES & VASCULAR DISEASE RESEARCH, 2013, 10 (04) :380-382
[2]  
Brennan Amanda L, 2004, J Cyst Fibros, V3, P209, DOI 10.1016/j.jcf.2004.08.001
[3]   The Receptor for Advanced Glycation End Products (RAGE) and the Lung [J].
Buckley, Stephen T. ;
Ehrhardt, Carsten .
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2010,
[4]   Standardised methodology of sputum induction and processing [J].
Djukanovic, R ;
Sterk, PJ ;
Fahy, JV ;
Hargreave, FE .
EUROPEAN RESPIRATORY JOURNAL, 2002, 20 :1S-2S
[5]   Plasma levels of soluble receptor for advanced glycation end products and coronary artery disease in nondiabetic men [J].
Falcone, C ;
Emanuele, E ;
D'Angelo, A ;
Buzzi, MP ;
Belvito, C ;
Cuccia, M ;
Geroldi, D .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (05) :1032-1037
[6]   Expression of S100A12 (EN-RAGE) in cystic fibrosis [J].
Foell, D ;
Seeliger, S ;
Vogl, T ;
Koch, HG ;
Maschek, H ;
Harms, E ;
Sorg, C ;
Roth, J .
THORAX, 2003, 58 (07) :613-617
[7]   The receptor for advanced glycation end products and acute lung injury/acute respiratory distress syndrome [J].
Guo, Weidun Alan ;
Knight, Paul R. ;
Raghavendran, Krishnan .
INTENSIVE CARE MEDICINE, 2012, 38 (10) :1588-1598
[8]   Identification, classification, and expression of RAGE gene splice variants [J].
Hudson, Barry I. ;
Carter, Angela M. ;
Harja, Evis ;
Kalea, Anastasia Z. ;
Arriero, Maria ;
Yang, Hojin ;
Grant, Peter J. ;
Schmidt, Ann Marie .
FASEB JOURNAL, 2008, 22 (05) :1572-1580
[9]   Blockade of receptor for advanced glycation endproducts: a new target for therapeutic intervention in diabetic complications and inflammatory disorders [J].
Hudson, BI ;
Bucciarelli, LG ;
Wendt, T ;
Sakaguchi, T ;
Lalla, E ;
Qu, W ;
Lu, Y ;
Lee, L ;
Stern, DM ;
Naka, Y ;
Ramasamy, R ;
Yan, SD ;
Yan, SF ;
D'Agati, V ;
Schmidt, AM .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2003, 419 (01) :80-88
[10]   Activation of critical, host-induced, metabolic and stress pathways marks neutrophil entry into cystic fibrosis lungs [J].
Makam, Megha ;
Diaz, Daisy ;
Laval, Julie ;
Gernez, Yael ;
Conrad, Carol K. ;
Dunn, Colleen E. ;
Davies, Zoe A. ;
Moss, Richard B. ;
Herzenberg, Leonore A. ;
Herzenberg, Leonard A. ;
Tirouvanziam, Rabindra .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (14) :5779-5783