title: Lipopolysaccharide induces a stromal-epithelial signalling axis in a rat model of chronic periodontitis.
abstract: OBJECTIVE
  Lipopolysaccharide is a bacterial virulence factor implicated in chronic periodontitis, which may penetrate the junctional epithelial barrier and basement membrane to insult underlying stroma. We sought to identify lipopolysaccharide-induced global gene expression changes responsible for signalling between stroma and epithelium during disease onset.
  
  
  METHODS
  Using a rat lipopolysaccharide periodontitis model, junctional epithelium and underlying stromal tissue were separately collected from healthy and diseased animals by laser-capture microdissection and subject to gene expression microarray analysis. Key gene products identified were validated in gingival epithelial and fibroblast cell cultures.
  
  
  RESULTS
  Global gene expression patterns distinguishing health versus disease were found in and between both tissue types. In stroma, the most significantly altered gene ontology function group (Z ≥ 4.00) was cytokines, containing most significantly (±2-fold; p < 0.05) upregulated genes amphiregulin, IL1-β and Fas ligand, all positive, diffusible modulators of the epithelial growth factor receptor pathway. In epithelium, the most significant changes were in downregulated FOS-related antigen-1 gene, somatostatin receptor-2 gene and mucin-4 gene, all negative modulators of the epithelial growth factor receptor pathway.
  
  
  CONCLUSIONS
  These results establish a periodontitis model for studying gene product interactions and suggests that the onset of junctional epithelial disease hyperproliferation involves a concerted stromal-epithelial signalling axis.
authors.affiliation: Department of Oral Biological & Medical Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: James D
authors.initials: JD
authors.lastname: Firth
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ekuni
authors.forename: Koichiro
authors.initials: K
authors.lastname: Irie
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tomofuji
authors.forename: Manabu
authors.initials: M
authors.lastname: Morita
authors.forename: Edward E
authors.initials: EE
authors.lastname: Putnins
mesh_terms: D066258:Amphiregulin; D000818:Animals; D002478:Cells, Cultured; D055113:Chronic Periodontitis / Q000378:metabolism* / Q000382:microbiology*; D066255:EGF Family of Proteins; D004846:Epithelial Attachment / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000502:physiology*; D053222:Fas Ligand Protein / Q000235:genetics; D005347:Fibroblasts; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D061346:Laser Capture Microdissection; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D055264:Mucin-4 / Q000235:genetics; D016966:Porphyromonas gingivalis / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D066258:Amphiregulin; C587850:Areg protein, rat; D066255:EGF Family of Proteins; D053222:Fas Ligand Protein; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D055264:Mucin-4; D016760:Proto-Oncogene Proteins c-fos; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2; D066246:ErbB Receptors