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Over‐expression of RAGE by proximal lung epithelial cells causes an inflammatory response in adult mice
Author(s) -
Bennion Brock G,
Bodine B Garrett,
Leatham Emma,
Wright Alex J,
Jergensen Zac R,
Erickson Connor J,
Jones Cameron M,
Johnson Jeff P,
Knapp Steven M,
Reynolds Paul R
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.137.12
Subject(s) - rage (emotion) , bronchoalveolar lavage , inflammation , receptor , lung , immunology , glycation , medicine , immunohistochemistry , biology , chemistry , neuroscience
Receptors for advanced glycation end‐products (RAGE) are multiligand cell‐surface receptors expressed abundantly by pulmonary epithelium. Our lab has discovered RAGE‐mediated effects in lung inflammation induced by tobacco smoke and environmental pollutants; however, the precise contribution of RAGE to proximal airway inflammation was yet unknown. We generated a Tet‐inducible transgenic mouse that conditionally over‐expresses RAGE using the Clara Cell Secretory Protein (CCSP) promoter active in proximal airway Clara cells. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Compared to controls, immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up‐regulation; however, H&E staining revealed no detectible morphological disturbances. Freshly procured bronchoalveolar lavage fluid (BALF) from RAGE TG mice had significantly greater total protein content, total leukocyte quantity, PMN abundance, and cytokine concentration compared to age‐matched control littermates. These data support the concept that RAGE up‐regulation in lung airways may participate in inflammation of the proximal airway. Supported by the Flight Attendant's Medical Research Institute (FAMRI, PRR) and a BYU MEG (PRR).