Cigarette smoke extract (CSE) induces RAGE-mediated inflammation in the Ca9-22 gingival carcinoma epithelial cell line

Arch Oral Biol. 2017 Aug:80:95-100. doi: 10.1016/j.archoralbio.2017.03.021. Epub 2017 Mar 31.


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.

Design: 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.

Keywords: CSE; Epithelium; Gingival; RAGE; Tobacco.

MeSH terms

  • Cell Line, Tumor
  • Cells, Cultured
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Gingival Neoplasms / metabolism*
  • Glycosaminoglycans / pharmacology
  • Humans
  • Immunoblotting
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • NF-kappa B / metabolism
  • Nicotiana / toxicity*
  • Real-Time Polymerase Chain Reaction
  • Receptor for Advanced Glycation End Products / metabolism*
  • Receptors, Immunologic / metabolism
  • Signal Transduction / drug effects
  • Smoke*


  • Cytokines
  • Glycosaminoglycans
  • Inflammation Mediators
  • NF-kappa B
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Smoke