Emphysema requires the receptor for advanced glycation end-products triggering on structural cells.

Published on Apr 1, 2015in American Journal of Respiratory Cell and Molecular Biology5.373
· DOI :10.1165/RCMB.2014-0027OC
Koichi Waseda9
Estimated H-index: 9
(Okayama University),
Nobuaki Miyahara33
Estimated H-index: 33
(RMIT: RMIT University)
+ 9 AuthorsArihiko Kanehiro25
Estimated H-index: 25
Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The receptor for advanced glycation end-products (RAGE) is a multiligand cell surface receptor reported to be involved in the process of acute alveolar epithelial cell injury. However, studies that address the role of RAGE in pulmonary emphysema are inconclusive. We investigated the role of RAGE in the development of elastase-induced pulmonary inflammation and emphysema in mice. RAGE-sufficient (RAGE+/+) mice and RAGE-deficient (RAGE−/−) mice were treated with intratracheal elastase on Day 0. Airway inflammation, static lung compliance, lung histology, and the levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage fluid were determined on Days 4 and 21. Neutrophilia in bronchoalveolar lavage fluid, seen in elastase-treated RAGE+/+ mice, was reduced in elastase-treated RAGE−/− mice on Day 4, and was associated with decreased levels of keratinocyte chemoattractant, ma...
📖 Papers frequently viewed together
32 Citations
157 Citations
#1Megan P. Stogsdill (BYU: Brigham Young University)H-Index: 3
Last. Paul R. ReynoldsH-Index: 24
view all 8 authors...
Receptors for advanced glycation end-products (RAGE) are multiligand surface receptors detected abundantly in pulmonary tissue. Our previous work revealed increased RAGE expression in cells and lungs exposed to tobacco smoke and RAGE-mediated cytokine expression via proinflammatory mechanisms involving NF-κB. RAGE expression is elevated in various pathological states, including chronic obstructive pulmonary disease; however, precise contributions of RAGE to the progression of emphysema and pulmo...
42 CitationsSource
#1Silvia Fineschi (UNISI: University of Siena)H-Index: 13
#2Giovanna De Cunto (UNISI: University of Siena)H-Index: 13
Last. Eleonora Cavarra (UNISI: University of Siena)H-Index: 22
view all 13 authors...
The role of the receptor for advanced glycation end products (RAGE) in promoting the inflammatory response through activation of NF-κB pathway is well established. Recent findings indicate that RAGE may also have a regulative function in apoptosis, as well as in cellular proliferation, differentiation, and adhesion. Unlike other organs, lung tissue in adulthood and during organ development shows relatively high levels of RAGE expression. Thus a role for the receptor in lung organogenesis and hom...
30 CitationsSource
#1Hikari Koga (Okayama University)H-Index: 8
#2Nobuaki Miyahara (Okayama University)H-Index: 33
Last. Arihiko Kanehiro (Okayama University)H-Index: 25
view all 11 authors...
Background Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in previously sensitized and c...
38 CitationsSource
#1Etsuko Kurimoto (Okayama University)H-Index: 6
#2Nobuaki Miyahara (Okayama University)H-Index: 33
Last. Mitsune Tanimoto (Okayama University)H-Index: 68
view all 13 authors...
Background Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it’s role in the inflammatory response of elastase-induced emphysema remains unclear.
67 CitationsSource
Receptors for advanced glycation end-products (RAGEs) are multiligand cell surface receptors highly expressed in the lung that contribute to alveolar epithelial cell differentiation during embryogenesis and the modulation of pulmonary inflammation during disease. When RAGEs are overexpressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. However, the possible mechanisms that lead to the disappearance of pulmonary tissue remain unclear. A time course ...
26 CitationsSource
#1Adam B. Robinson (BYU: Brigham Young University)H-Index: 5
#2KacyAnn D. Johnson (BYU: Brigham Young University)H-Index: 1
Last. Paul R. Reynolds (BYU: Brigham Young University)H-Index: 24
view all 4 authors...
Receptors for advanced glycation end-products (RAGE) are multiligand cell surface receptors of the immunoglobin family expressed by epithelium and macrophages, and expression increases following exposure to cigarette smoke extract (CSE). The present study sought to characterize the proinflammatory contributions of RAGE expressed by alveolar macrophages (AMs) following CSE exposure. Acute exposure of mice to CSE via nasal instillation revealed diminished bronchoalveolar lavage (BAL) cellularity a...
52 CitationsSource
#1Maria B. Sukkar (USYD: University of Sydney)H-Index: 30
#2Lisa WoodH-Index: 77
Last. Peter A. B. WarkH-Index: 59
view all 7 authors...
The receptor for advanced glycation end-products (RAGE) is a pattern-recognition receptor involved in the host response to injury, infection and inflammation. It is a membrane receptor, but also has soluble forms (sRAGE). Deficiencies in sRAGE are linked to heightened inflammation in various chronic conditions. We determined whether airway and systemic levels of sRAGE and the RAGE ligands HMGB1 (high-mobility group box-1) and serum amyloid A (SAA) are related to neutrophilic inflammation in asth...
93 CitationsSource
#1Yasuko Fuchimoto (Okayama University)H-Index: 9
#2Arihiko KanehiroH-Index: 25
Last. Mitsune TanimotoH-Index: 68
view all 11 authors...
Chemokine receptor (CCR) 5 is expressed on dendritic cells, macrophages, CD8 cells, memory CD4 T cells, and stromal cells, and is frequently used as a marker of T helper type 1 cells. Interventions that abrogate CCR5 or interfere with its ligand binding have been shown to alter T helper type 2–induced inflammatory responses. The role of CCR5 on allergic airway responses is not defined. CCR5-deficient (CCR5−/−) and wild-type (CCR5+/+) mice were sensitized and challenged with ovalbumin (OVA) and a...
13 CitationsSource
#1Koichi WasedaH-Index: 9
#2Nobuaki Miyahara (RMIT: RMIT University)H-Index: 33
Last. Erwin W. Gelfand (University of Colorado Denver)H-Index: 113
view all 11 authors...
Most of the studies investigating the effectiveness of blocking the leukotriene B4 (LTB4) receptor 1 (BLT1) have been performed in models of primary or acute allergen challenge. The role of the LTB4-BLT1 pathway in secondary challenge models, where airway hyperresponsiveness (AHR) and airway inflammation have been established, has not been defined. We investigated the effects of blocking BLT1 on early- and late-phase development of AHR and airway inflammation in previously sensitized and challen...
14 CitationsSource
#1Paul R. Reynolds (BYU: Brigham Young University)H-Index: 24
#2Stephen D. Kasteler (UofU: University of Utah)H-Index: 4
Last. John R. HoidalH-Index: 84
view all 4 authors...
We previously demonstrated up-regulation of the receptor for advanced glycation end-products (RAGE) and its ligands by cigarette smoke extract (CSE) in rat R3/1 cells, a type I–like alveolar epithelial cell line. However, RAGE-mediated intracellular signaling pathways that lead to pulmonary inflammation remained unclear. Using ELISAs, we demonstrate that alveolar epithelial cell lines exposed to 25% CSE for 2 hours induce the activation of Ras, a small GTPase that functions as a molecular switch...
59 CitationsSource
Cited By16
#1Venkata Sita Rama Raju Allam (UTS: University of Technology, Sydney)H-Index: 2
#2Alen Faiz (UTS: University of Technology, Sydney)H-Index: 17
Last. Maria B. Sukkar (UTS: University of Technology, Sydney)H-Index: 30
view all 17 authors...
Background The receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) is implicated in COPD. Although these receptors share common ligands and signalling pathways, it is not known whether they act in concert to drive pathological processes in COPD. We examined the impact of RAGE and/or TLR4 gene deficiency in a mouse model of COPD and also determined whether expression of these receptors correlates with airway neutrophilia and airway hyperresponsiveness (AHR) in COPD...
#1Syed Hissam Haider (NYU: New York University)H-Index: 6
#2Arul Veerappan (NYU: New York University)H-Index: 4
Last. Anna Nolan (FDNY: New York City Fire Department)H-Index: 22
view all 14 authors...
Pulmonary disease after World Trade Center particulate matter(WTC-PM) exposure is associated with dyslipidemia and the receptor for advanced glycation end products (RAGE); however, the mechanisms are not well understood. We utilized a murine model and a multiOMIC assessment to understand the role of RAGE in the pulmonary long-term effects of a single high intensity exposure to WTC-PM. After 1-month(1-M), WTC-PM exposed wild-type(WT) mice had airway hyperreactivity(AHR) while RAGE-deficient(Ager-...
3 CitationsSource
#1Giovanna De Cunto (UNISI: University of Siena)H-Index: 13
#2Eleonora Cavarra (UNISI: University of Siena)H-Index: 22
Last. Monica Lucattelli (UNISI: University of Siena)H-Index: 2
view all 5 authors...
COPD can manifest itself with different clinical phenotypes characterized by different disease progression and response to therapy. Although a remarkable number of studies have been carried out, little is known about the mechanisms underlying phenotypes that could guide the development of viable future therapies. Several murine strains mirror some human phenotypes after smoke exposure. It was of interest to investigate in these strains whether different pattern of activation of macrophages, and ...
#1Giovanna De Cunto (UNISI: University of Siena)H-Index: 13
#2Eleonora Cavarra (UNISI: University of Siena)H-Index: 22
Last. Giuseppe Lungarella (UNISI: University of Siena)H-Index: 40
view all 5 authors...
Chronic obstructive pulmonary disease (COPD) is mainly associated with smoking habit. Inflammation is the major initiating process whereby neutrophils and monocytes are attracted into the lung microenvironment by external stimuli present in tobacco leaves and in cigarette smoke, which promote chemotaxis, adhesion, phagocytosis, release of superoxide anions and enzyme granule contents. A minority of smokers develops COPD and different molecular factors, which contribute to the onset of the diseas...
2 CitationsSource
#1Ting Yang (Sichuan University)H-Index: 28
#2Hao Wang (Sichuan University)H-Index: 108
Last. Fuqiang Wen (Sichuan University)H-Index: 23
view all 10 authors...
Abstract Background Cigarette smoke plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Recently, elevated serotonin (5-HT) levels were found in the plasma of COPD patients. The role of 5-HT and its receptors in airway inflammation and remodeling induced by cigarette smoke is unclear. Methods BALB/c mice received the 5-HTR2A inhibitor ketanserin, the 5-HTR2B inhibitor RS-127445 or the natural 5-HTR2A/2B inhibitor quercetin intraperitoneally, then were exp...
4 CitationsSource
#1Kary Y. F. Tsai (BYU: Brigham Young University)H-Index: 2
#2Kelsey M. Hirschi Budge (BYU: Brigham Young University)H-Index: 1
Last. Paul R. Reynolds (BYU: Brigham Young University)H-Index: 24
view all 9 authors...
AbstractAim and Purpose: Tobacco exposure is one of the top three global health risks leading to the development of chronic obstructive pulmonary disease (COPD). Although there is extensive researc...
2 CitationsSource
#1Naohiro Oda (Okayama University)H-Index: 8
#2X. Nobuaki Miyahara (RMIT: RMIT University)H-Index: 1
Last. Yoshinobu Maeda (Okayama University)H-Index: 29
view all 11 authors...
Neuropeptide Y (NPY) is a neurotransmitter that is widely expressed in the brain and peripheral nervous system. Various immune cells express the NPY Y1 receptor. NPY modulates these cells via its Y...
3 CitationsSource
#1Karl Sanders (UofU: University of Utah)H-Index: 14
#2Don A. Delker (UofU: University of Utah)H-Index: 19
Last. John R. Hoidal (UofU: University of Utah)H-Index: 84
view all 9 authors...
The receptor for advanced glycation end products (RAGE), a cell membrane receptor, recognizes ligands produced by cigarette smoke (CS) and has been implicated in the pathogenesis of COPD. We demonstrate that deletion or pharmacologic inhibition of RAGE prevents development of CS-induced emphysema. To identify molecular pathways by which RAGE mediates smoking related lung injury we performed unbiased gene expression profiling of alveolar macrophages (AM) obtained from RAGE null and C57BL/6 WT mic...
14 CitationsSource
#1Erin J. Caraher (NYU: New York University)H-Index: 6
#2Sophia Kwon (NYU: New York University)H-Index: 13
Last. Anna Nolan (NYU: New York University)H-Index: 22
view all 13 authors...
World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-i...
18 CitationsSource
#1Lisa Wolf (Saarland University)H-Index: 7
#2Christian Herr (Saarland University)H-Index: 24
Last. Robert Bals (Saarland University)H-Index: 66
view all 5 authors...
The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased r...
22 CitationsSource