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
  • [1] INTERLEUKIN-7 - BIOLOGY AND POTENTIAL CLINICAL-APPLICATIONS
    APPASAMY, PM
    [J]. CANCER INVESTIGATION, 1993, 11 (04) : 487 - 499
  • [2] Smoking and asthma -: Clinical and radiologic features, lung function, and airway inflammation
    Boulet, LP
    Lemière, C
    Archambault, F
    Carrier, G
    Descary, MC
    Deschesnes, F
    [J]. CHEST, 2006, 129 (03) : 661 - 668
  • [3] The Receptor for Advanced Glycation End Products (RAGE) and the Lung
    Buckley, Stephen T.
    Ehrhardt, Carsten
    [J]. JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2010,
  • [4] Development of a mouse model mimicking key aspects of a viral asthma exacerbation
    Clarke, Deborah L.
    Davis, Nicola H. E.
    Majithiya, Jayesh B.
    Piper, Sian C.
    Lewis, Arthur
    Sleeman, Matthew A.
    Corkill, Dominic J.
    May, Richard D.
    [J]. CLINICAL SCIENCE, 2014, 126 (7-8) : 567 - 580
  • [5] Promotion of cell adherence and spreading: a novel function of RAGE, the highly selective differentiation marker of human alveolar epithelial type I cells
    Demling, N
    Ehrhardt, C
    Kasper, M
    Laue, M
    Knels, L
    Rieber, EP
    [J]. CELL AND TISSUE RESEARCH, 2006, 323 (03) : 475 - 488
  • [6] Cell cycle: Routine role for Ras
    Downward, J
    [J]. CURRENT BIOLOGY, 1997, 7 (04) : R258 - R260
  • [7] Use of human bronchial epithelial cells (BEAS-2B) to study immunological markers resulting from exposure to PM2.5 organic extract from Puerto Rico
    Fuentes-Mattei, Enrique
    Rivera, Evasomary
    Gioda, Adriana
    Sanchez-Rivera, Diana
    Roman-Velazquez, Felix R.
    Jimenez-Velez, Braulio D.
    [J]. TOXICOLOGY AND APPLIED PHARMACOLOGY, 2010, 243 (03) : 381 - 389
  • [8] Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation
    Bowman, M. A. Hofmann
    Heydemann, A.
    Gawdzik, J.
    Shilling, R. A.
    Camoretti-Mercado, B.
    [J]. CLINICAL AND EXPERIMENTAL ALLERGY, 2011, 41 (06) : 878 - 889
  • [9] Idriss HT, 2000, MICROSC RES TECHNIQ, V50, P184, DOI 10.1002/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO
  • [10] 2-H