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Downregulation of toll‐like receptor‐mediated signalling pathways in oral lichen planus
Author(s) -
Si Suraya H.,
Rich Alison M.,
Parachuru Venkata P. B.,
Firth Fiona A.,
Milne Trudy,
Seymour Gregory J.
Publication year - 2016
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12319
Subject(s) - oral lichen planus , downregulation and upregulation , tlr2 , tlr4 , immunohistochemistry , receptor , biology , tlr3 , toll like receptor , immune system , immunology , cancer research , microbiology and biotechnology , medicine , gene , innate immune system , biochemistry
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.