title: Downregulation of toll-like receptor-mediated signalling pathways in oral lichen planus.
abstract: OBJECTIVE
  The objective of this study was to investigate the expression of Toll-like receptors (TLR) and TLR-associated signalling pathway genes in oral lichen planus (OLP).
  
  
  METHODS
  Initially, immunohistochemistry was used to determine TLR expression in 12 formalin-fixed archival OLP tissues with 12 non-specifically inflamed oral tissues as controls. RNA was isolated from further fresh samples of OLP and non-specifically inflamed oral tissue controls (n = 6 for both groups) and used in qRT(2)-PCR focused arrays to determine the expression of TLRs and associated signalling pathway genes. Genes with a statistical significance of ±two-fold regulation (FR) and a P-value < 0.05 were considered as significantly regulated.
  
  
  RESULTS
  Significantly more TLR4(+) cells were present in the inflammatory infiltrate in OLP compared with the control tissues (P < 0.05). There was no statistically significant difference in the numbers of TLR2(+) and TLR8(+) cells between the groups. TLR3 was significantly downregulated in OLP (P < 0.01). TLR8 was upregulated in OLP, but the difference between the groups was not statistically significant. The TLR-mediated signalling-associated protein genes MyD88 and TIRAP were significantly downregulated (P < 0.01 and P < 0.05), as were IRAK1 (P < 0.05), MAPK8 (P < 0.01), MAP3K1 (P < 0.05), MAP4K4 (P < 0.05), REL (P < 0.01) and RELA (P < 0.01). Stress proteins HMGB1 and the heat shock protein D1 were significantly downregulated in OLP (P < 0.01).
  
  
  CONCLUSIONS
  These findings suggest a downregulation of TLR-mediated signalling pathways in OLP lesions.
authors: Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur, Malaysia.
authors: Suraya H
authors: SH
authors: Sinon
authors: The Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.
authors: Alison M
authors: AM
authors: Rich
authors: The Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.
authors: Venkata P B
authors: VP
authors: Parachuru
authors: The Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.
authors: Fiona A
authors: FA
authors: Firth
authors: The Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.
authors: Trudy
authors: T
authors: Milne
authors: The Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.
authors: Gregory J
authors: GJ
authors: Seymour
mesh_terms: D015536:Down-Regulation; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017676:Lichen Planus, Oral / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D018840:HSP70 Heat-Shock Proteins; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; D051193:Toll-Like Receptors
keywords: Toll-like receptors; oral lichen planus