title: Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation.
abstract: 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.
  
  
  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-α), 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.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. gbodine14@gmail.com.
authors.forename: B Garrett
authors.initials: BG
authors.lastname: Bodine
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. brock.bennion@gmail.com.
authors.forename: Brock G
authors.initials: BG
authors.lastname: Bennion
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. emmathemormon@yahoo.com.
authors.forename: Emma
authors.initials: E
authors.lastname: Leatham
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. felixrjr2006@gmail.com.
authors.forename: Felix R
authors.initials: FR
authors.lastname: Jimenez
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. alex20wright@gmail.com.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Wright
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. zjergensen@gmail.com.
authors.forename: Zac R
authors.initials: ZR
authors.lastname: Jergensen
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. cericksen_biker@hotmail.com.
authors.forename: Connor J
authors.initials: CJ
authors.lastname: Erickson
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. cmacjonesy@gmail.com.
authors.forename: Cameron M
authors.initials: CM
authors.lastname: Jones
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. jeffreypacejohnson@gmail.com.
authors.forename: Jeff P
authors.initials: JP
authors.lastname: Johnson
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. knapster99@yahoo.com.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Knapp
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, 3054 Life Sciences Building, Provo, UT, 84602, USA. paul_reynolds@byu.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Reynolds
mesh_terms: D056809:Alveolar Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D005838:Genotype; D018836:Inflammation Mediators / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration; D010641:Phenotype; D011014:Pneumonia / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014598:Uteroglobin / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: D018836:Inflammation Mediators; D015851:Interleukin-7; D007378:Interleukins; D000067759:Receptor for Advanced Glycation End Products; C545985:TXLNA protein, mouse; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; C576410:interleukin-7, mouse; D014598:Uteroglobin