Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation

被引:11
作者
Bodine, B. Garrett [1 ]
Bennion, Brock G. [1 ]
Leatham, Emma [1 ]
Jimenez, Felix R. [1 ]
Wright, Alex J. [1 ]
Jergensen, Zac R. [1 ]
Erickson, Connor J. [1 ]
Jones, Cameron M. [1 ]
Johnson, Jeff P. [1 ]
Knapp, Steven M. [1 ]
Reynolds, Paul R. [1 ]
机构
[1] Brigham Young Univ, Dept Physiol & Dev Biol, 3054 Life Sci Bldg, Provo, UT 84602 USA
关键词
RAGE; Transgenic; CCSP; Lung; Inflammation; GLYCATION END-PRODUCTS; MOUSE MODEL; TNF-ALPHA; ASTHMA; RECEPTORS; SMOKING; GROWTH; OVEREXPRESSION;
D O I
10.1186/s12931-014-0133-y
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background: Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized. Methods and results: We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-alpha), interleukin 7 (IL-7), and interleukin 14 (IL-14) in whole lung homogenates compared to controls. Conclusions: These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.
引用
收藏
页数:9
相关论文
共 47 条
[21]   A study of twelve southern California communities with differing levels and types of air pollution - I. Prevalence of respiratory morbidity [J].
Peters, JM ;
Avol, E ;
Navidi, W ;
London, SJ ;
Gauderman, WJ ;
Lurmann, F ;
Linn, WS ;
Margolis, H ;
Rappaport, E ;
Gong, H ;
Thomas, DC .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1999, 159 (03) :760-767
[22]   Low anticoagulant heparin targets multiple sites of inflammation, suppresses heparin-induced thrombocytopenia, and inhibits interaction of RAGE with its ligands [J].
Rao, Narayanam V. ;
Argyle, Brian ;
Xu, Xiaoyu ;
Reynolds, Paul R. ;
Walenga, Jeanine M. ;
Prechel, Margaret ;
Prestwich, Glenn D. ;
MacArthur, Robert B. ;
Walters, Bradford B. ;
Hoidal, John R. ;
Kennedy, Thomas P. .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2010, 299 (01) :C97-C110
[23]   RAGE: developmental expression and positive feedback regulation by Egr-1 during cigarette smoke exposure in pulmonary epithelial cells [J].
Reynolds, Paul R. ;
Kasteler, Stephen D. ;
Cosio, Manuel G. ;
Sturrock, Anne ;
Huecksteadt, Tom ;
Hoidal, John R. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2008, 294 (06) :L1094-L1101
[24]   Up-Regulation of Receptors for Advanced Glycation End-Products by Alveolar Epithelium Influences Cytodifferentiation and Causes Severe Lung Hypoplasia [J].
Reynolds, Paul R. ;
Stogsdill, Jeffrey A. ;
Stogsdill, Megan P. ;
Heimann, Nicholas B. .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2011, 45 (06) :1195-1202
[25]   Receptor for Advanced Glycation End-Products Signals through Ras during Tobacco Smoke-Induced Pulmonary Inflammation [J].
Reynolds, Paul R. ;
Kasteler, Stephen D. ;
Schmitt, Robert E. ;
Hoidal, John R. .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2011, 45 (02) :411-418
[26]   Diesel Particulate Matter Induces Receptor for Advanced Glycation End-Products (RAGE) Expression in Pulmonary Epithelial Cells, and RAGE Signaling Influences NF-κB-Mediated Inflammation [J].
Reynolds, Paul R. ;
Wasley, Karisa M. ;
Allison, Camille H. .
ENVIRONMENTAL HEALTH PERSPECTIVES, 2011, 119 (03) :332-336
[27]   Receptors for Advanced Glycation End-Products Targeting Protect against Hyperoxia-Induced Lung Injury in Mice [J].
Reynolds, Paul R. ;
Schmitt, Robert E. ;
Kasteler, Stephen D. ;
Sturrock, Anne ;
Sanders, Karl ;
Bierhaus, Angelika ;
Nawroth, Peter P. ;
Paine, Robert, III ;
Hoidal, John R. .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2010, 42 (05) :545-551
[28]   Midkine is regulated by hypoxia and causes pulmonary vascular remodeling [J].
Reynolds, PR ;
Mucenski, ML ;
Le Cras, TD ;
Nichols, WC ;
Whitsett, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (35) :37124-37132
[29]   RAGE and tobacco smoke: insights into modeling chronic obstructive pulmonary disease [J].
Robinson, Adam B. ;
Stogsdill, Jeffrey A. ;
Lewis, Joshua B. ;
Woodand, Tyler T. ;
Reynolds, Paul R. .
FRONTIERS IN PHYSIOLOGY, 2012, 3
[30]   RAGE signaling by alveolar macrophages influences tobacco smoke-induced inflammation [J].
Robinson, Adam B. ;
Johnson, KacyAnn D. ;
Bennion, Brock G. ;
Reynolds, Paul R. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2012, 302 (11) :L1192-L1199