title: Expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 protein (Fn14), in healthy tissues and in tissues affected by periodontitis.
abstract: OBJECTIVE
  Host-derived enzymes, cytokines and other proinflammatory mediators play an integral role in periodontal destruction. The levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 protein (Fn14), are elevated in tissues from a number of chronic inflammatory diseases. The aim of the present study was to investigate the expression of TWEAK and Fn14 at the protein and mRNA levels in gingival biopsies from periodontitis patients and from clinically healthy patients.
  
  
  METHODS
  Gingival biopsies were obtained from healthy sites (n = 7) and from sites affected by periodontitis (n = 27). The expression of TWEAK and Fn14 was investigated by immunohistochemistry in formalin-fixed, paraffin-embedded tissues. The levels of mRNA for TWEAK and Fn14 were also investigated by RT-PCR.
  
  
  RESULTS
  The expression of TWEAK and Fn14 proteins was significantly higher in periodontitis tissue than in healthy tissue. In periodontitis tissues, TWEAK and Fn14 proteins were mainly expressed by mononuclear leukocytes (morphologically resembling lymphocytes and plasma cells), by cells lining blood vessels, by spindle-shaped cells resembling fibroblasts and by multinucleated cells. The Fn14 mRNA level in periodontitis tissue was significantly higher than that in healthy tissue. A moderate correlation between TWEAK/Fn14 expression and inflammation and bone loss, but not pocket depth, was noted.
  
  
  CONCLUSIONS
  This study demonstrates higher expression of TWEAK protein and of Fn14 mRNA and protein in periodontitis tissues than in clinically healthy controls. Our data support the concept that TWEAK/Fn14 signaling is an additional player in the pathogenesis of periodontitis and adds to the increasing number of cytokine networks involved in periodontal inflammation.
authors.affiliation: Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, Adelaide, SA, Australia.
authors.forename: N G
authors.initials: NG
authors.lastname: Kataria
authors.forename: P M
authors.initials: PM
authors.lastname: Bartold
authors.forename: A A S K
authors.initials: AA
authors.lastname: Dharmapatni
authors.forename: G J
authors.initials: GJ
authors.lastname: Atkins
authors.forename: C A
authors.initials: CA
authors.lastname: Holding
authors.forename: D R
authors.initials: DR
authors.lastname: Haynes
mesh_terms: D000328:Adult; D000368:Aged; D010520:Aggressive Periodontitis / Q000473:pathology*; D016301:Alveolar Bone Loss / Q000473:pathology; D017209:Apoptosis / Q000502:physiology*; D001706:Biopsy; D055113:Chronic Periodontitis / Q000473:pathology*; D000074049:Cytokine TWEAK; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005881:Gingiva / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008024:Ligands; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017622:Periodontal Attachment Loss / Q000473:pathology; D010514:Periodontal Pocket / Q000473:pathology; D010950:Plasma Cells / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000032:analysis*; D055815:Young Adult
chemical_list: D000074049:Cytokine TWEAK; D008024:Ligands; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors