title: Cigarette smoke extract (CSE) induces RAGE-mediated inflammation in the Ca9-22 gingival carcinoma epithelial cell line.
abstract: OBJECTIVE
  The oral environment is anatomically positioned as a significant gateway for exposure to environmental toxicants. Cigarette smoke exposure compromises oral health by orchestrating inflammation. The receptor for advanced glycation end-products (RAGE) has been implicated in smoke-induced inflammatory effects; however, its role in the oral cavity is unknown. The purpose of this study was to determine RAGE expression by immortalized gingival carcinoma cells and the degree to which RAGE-mediated signaling influences inflammation.
  
  
  METHODS
  Gingival epithelia cells (Ca9-22) were exposed to 10% cigarette smoke extract (CSE) for six hours and screened for RAGE expression and inflammatory mediators.
  
  
  RESULTS
  Quantitative PCR and immunoblotting revealed increased RAGE expression following exposure. Furthermore, exposure activated RAGE signaling intermediates including Ras and NF-κB. IL-6 and IL-1β were also elevated in cell culture medium from CSE-exposed cells when compared to controls. A family of anionic, partially lipophilic sulfated polysaccharide derivatives known as semi-synthetic glycosaminoglycan ethers (SAGEs) were used in an effort to block RAGE signaling. Co-treatment of CSE and SAGEs ameliorated inflammatory responses.
  
  
  CONCLUSIONS
  These results provide a new perspective on a mechanism of cigarette smoke induced oral inflammation. Further work may show RAGE signaling as a potential target in the treatment of diseases of the oral cavity exacerbated by tobacco smoke exposure.
authors.affiliation: College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA.
authors.forename: Nolan T
authors.initials: NT
authors.lastname: Sanders
authors.affiliation: College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Dutson
authors.affiliation: College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA.
authors.forename: Justin W
authors.initials: JW
authors.lastname: Durrant
authors.affiliation: Lung and Placenta Research Laboratory, Brigham Young University, Physiology and Developmental Biology, Provo, UT, USA.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Lewis
authors.affiliation: College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA.
authors.forename: Shalene H
authors.initials: SH
authors.lastname: Wilcox
authors.affiliation: College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT, USA.
authors.forename: Duane R
authors.initials: DR
authors.lastname: Winden
authors.affiliation: Lung and Placenta Research Laboratory, Brigham Young University, Physiology and Developmental Biology, Provo, UT, USA.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Arroyo
authors.affiliation: Laboratory of Obesity and Metabolism, Brigham Young University, Physiology and Developmental Biology, Provo, UT, USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Bikman
authors.affiliation: Lung and Placenta Research Laboratory, Brigham Young University, Physiology and Developmental Biology, Provo, UT, USA. Electronic address: paul_reynolds@byu.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Reynolds
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005887:Gingival Neoplasms / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke; D062789:Tobacco Products
chemical_list: D016207:Cytokines; D006025:Glycosaminoglycans; D018836:Inflammation Mediators; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012906:Smoke
keywords: CSE; Epithelium; Gingival; RAGE; Tobacco