Downregulation of toll-like receptor-mediated signalling pathways in oral lichen planus

J Oral Pathol Med. 2016 Jan;45(1):28-34. doi: 10.1111/jop.12319. Epub 2015 Apr 12.


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).

Conclusion: These findings suggest a downregulation of TLR-mediated signalling pathways in OLP lesions.

Keywords: Toll-like receptors; oral lichen planus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Down-Regulation
  • Female
  • HMGB1 Protein / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Lichen Planus, Oral / genetics
  • Lichen Planus, Oral / metabolism*
  • Lichen Planus, Oral / pathology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Mouth Mucosa / metabolism
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism
  • Signal Transduction
  • Toll-Like Receptors / biosynthesis
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*
  • Up-Regulation


  • HMGB1 Protein
  • HMGB1 protein, human
  • HSP70 Heat-Shock Proteins
  • MYD88 protein, human
  • Membrane Glycoproteins
  • Myeloid Differentiation Factor 88
  • Receptors, Interleukin-1
  • TIRAP protein, human
  • Toll-Like Receptors