Gene and protein localisation of tumour necrosis factor (TNF)-α converting enzyme in gingival tissues from periodontitis patients with drug-induced gingival overgrowth

Arch Oral Biol. 2013 Aug;58(8):1014-20. doi: 10.1016/j.archoralbio.2013.02.011. Epub 2013 Mar 16.

Abstract

Objective: It is known that tumour necrosis factor (TNF)-α converting enzyme (TACE) plays a crucial role in fibrotic inflammatory diseases, and is specifically inhibited by tissue inhibitor of metalloproteinase (TIMP)-3. Fibrotic drug-induced gingival overgrowth (GO) is often combined with periodontitis. However, neither TACE nor TIMP-3 has been thoroughly examined in periodontal tissues to date. The aim of the present study was to analyse mRNA expression of TACE and TIMP-3, and protein localisation of TACE in gingival tissues removed from drug-(calcium-channel blocker) induced GO and periodontitis.

Methods: A total of 30 gingival tissue samples were taken from 15 GO and 15 periodontitis patients. The mRNA expression levels were analysed by quantitative reverse transcription polymerase chain-reaction (qRT-PCR) and the protein localisation was investigated by immunohistochemistry. Statistical analysis was performed using the Mann-Whitney U-test.

Results: TACE and TIMP-3 mRNA levels were significantly higher in GO compared to the periodontitis groups, as revealed by qRT-PCR (p<0.05). TACE-producing cells were immunohistochemically detected among monocytes/macrophages, plasma cells and some epithelial cells. TACE immunoreactivity was shown to be more intense in GO than in periodontitis-gingival tissue.

Conclusions: We have demonstrated TACE expression in cells such as macrophages, plasma cells and epithelial cells, and its predominant expression in GO tissues. This data suggests that TACE expression in GO-gingiva could be involved in the pathogenesis of disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / analysis
  • ADAM Proteins / genetics*
  • ADAM17 Protein
  • Calcium Channel Blockers / adverse effects
  • Epithelial Cells / pathology
  • Female
  • Gingiva / pathology*
  • Gingival Overgrowth / chemically induced*
  • Gingival Overgrowth / pathology
  • Humans
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Monocytes / pathology
  • Periodontal Attachment Loss / pathology
  • Periodontal Index
  • Periodontal Pocket / pathology
  • Periodontitis / genetics
  • Periodontitis / pathology*
  • Plasma Cells / pathology
  • Protease Inhibitors / analysis
  • RNA, Messenger / analysis
  • Tissue Inhibitor of Metalloproteinase-3 / analysis

Substances

  • Calcium Channel Blockers
  • Protease Inhibitors
  • RNA, Messenger
  • TIMP3 protein, human
  • Tissue Inhibitor of Metalloproteinase-3
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human