title: Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice.
abstract: The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in proinflammatory signaling, and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short-term secondhand smoke (SHS) exposure in RAGE knockout and control mice compared with identical animals exposed to room air only. Quantitative PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after 4 wk of SHS exposure and an anticipated absence of RAGE expression in RAGE knockout mice regardless of smoke exposure. Ras activation, NF-κB activity, and cytokine elaboration were assessed to characterize the molecular basis of SHS-induced inflammation in the mouse lung. Furthermore, bronchoalveolar lavage fluid was procured from RAGE knockout and control animals for the assessment of inflammatory cells and molecules. As a general theme, inflammation coincident with leukocyte recruitment was induced by SHS exposure and significantly influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to SHS. However, ongoing research is still warranted to fully explain roles for RAGE and other receptors in cells coping with involuntary smoke exposure for prolonged periods of time.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
authors.forename: Tyler T
authors.initials: TT
authors.lastname: Wood
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
authors.forename: Duane R
authors.initials: DR
authors.lastname: Winden
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
authors.forename: Derek R
authors.initials: DR
authors.lastname: Marlor
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Wright
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
authors.forename: Cameron M
authors.initials: CM
authors.lastname: Jones
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
authors.forename: Michael
authors.initials: M
authors.lastname: Chavarria
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
authors.forename: Geraldine D
authors.initials: GD
authors.lastname: Rogers
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah paul_reynolds@byu.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Reynolds
mesh_terms: D000208:Acute Disease; D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014028:Tobacco Smoke Pollution; D018631:ras Proteins
keywords: RAGE; inflammation; lung; secondhand smoke