title: Association of pocket epithelial cell proliferation in periodontitis with TLR9 expression and inflammatory response.
abstract: OBJECTIVE
  Inflammatory response is triggered after recognition of microbial ligands by innate receptors such as Toll-like receptors (TLRs) and Nucleotide oligomerization domain (NOD)-like receptors (NLRs). In this study, we examined serial frozen sections of gingival biopsies from patients with gingivitis or periodontitis by immunohistochemical analysis for the topographic expression patterns of selected innate receptors and their association with cell proliferation in clinically healthy and diseased gingival tissues.
  
  
  METHODS
  A total of 19 gingival biopsies were collected from patients at the School of Dentistry, National Taiwan University Medical Center according to approved protocol and with informed consent. The specimens were assigned to either the gingivitis group or periodontitis group after clinical evaluation using gingival index. Frozen sections of gingival biopsies were stained with hematoxylin and eosin for histological evaluation. Serial sections of the same samples were stained with a panel of antibodies for immunohistochemical analysis. Expression of each protein marker was compared in the oral versus the sulcular epithelium of the same section.
  
  
  RESULTS
  Expression of cytokeratin 19 (CK19) was markedly increased in the basement membranes of the oral epithelium and in all layers of the pocket epithelium where it caused evident cell proliferation and migration of sulcular epithelial cells into the lamina propria of periodontitis tissue. TLR4 and the cytoplasmic NLRP3 were expressed in all sections examined regardless of disease state. However, expression of TLR9-, CK19- and collagenolytic matrix metalloproteinase-13 and activated NF-κB subunit p65 was more commonly found in periodontitis tissues than in gingivitis tissues.
  
  
  CONCLUSIONS
  Activation of TLR9 signaling in the pocket epithelium was highly associated with periodontal inflammation and possibly with loss of tissue integrity. Further studies of mechanisms by which TLR9 signaling is activated in the periodontal epithelium may lead to new strategies for treating periodontitis.
authors.affiliation: Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Dentistry, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Cheing-Meei
authors.initials: CM
authors.lastname: Liu
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Jiiang-Huei
authors.initials: JH
authors.lastname: Jeng
authors.affiliation: Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: chiachiku@ntu.edu.tw.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Ku
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000473:pathology*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005881:Gingiva / Q000473:pathology*; D005891:Gingivitis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010518:Periodontitis / Q000235:genetics*; D013624:Taiwan; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
keywords: Toll-like receptors; gingival epithelium; immunohisto-chemistry; matrix metalloproteinase 13; periodontitis