Altered Expression of Toll-like Receptors in Human Oral Epithelium in Oral Lichenoid Reactions

Abstract

Oral lichenoid reactions (OLRs) are chronic inflammatory lesions induced by contact with allergens. Toll-like receptors (TLRs) are members of pattern-recognition receptor superfamily. Once activated, TLRs induce production of cytokines and chemokines, thus leading to inflammatory reaction in host tissue. In the present study, we aimed to investigate the potential role of TLRs in the initiation and perpetuation of OLRs, in which TLRs induce innate immune responses mounted against allergens. TLRs, 1 through 10, were mapped in tissue samples obtained from healthy donors and OLR patients using real-time quantitative reverse transcription polymerase chain reaction, immunostaining, and image analyses. We found that the immunoreactivity for all TLRs was increased in OLRs, except for TLR5, which was noticeably reduced. Gene analysis revealed that TLR1, TLR2, TLR4, TLR7, TLR8, and TLR9 transcripts were upregulated in OLRs compared with controls. In contrast, expression of TLR3, TLR5, and TLR6 genes were negatively regulated in OLRs. TLR10 remained unchanged in both groups. In conclusion, TLRs expression is deranged in OLRs in which TLRs could be sensitized by allergens and haptens derived from dental restorations. TLR reactivity is further enhanced by recruitment of T lymphocytes forming a diffuse lymphocytic infiltrate and thus creating a proinflammatory loop cycle. These findings suggest that TLRs are involved in OLRs and pave the way for alternative cost-effective therapeutic intervention.

Role of the high mobility group box 1 signalling axes via the receptor for advanced glycation end‐products and toll‐like receptor‐4 in the immunopathology of oral lichen planus: a potential drug target?

“…It is noteworthy that TLR4 antibody significantly reduces the HMGB1‐mediated release of cytokines by immune cells, such as macrophages . Such highly upregulated TLR4 status in OLP lesions may indicate involvement of the HMGB1‐TLR4 axis in OLP, which may contribute to disease chronicity . However, the results should be interpreted with caution as TLR4 upregulation in OLP could also be ascribed to various DAMPs/pathogen‐associated molecular patterns (PAMPs) other than HMGB1 (e.g.…”

“…The TLR4/MD‐2 complex is a vital component for HMGB1‐induced cytokine production and inflammation . Recently, we showed that TLR4 is upregulated in oral lichenoid lesions . It is noteworthy that TLR4 antibody significantly reduces the HMGB1‐mediated release of cytokines by immune cells, such as macrophages .…”

Histamine H4 receptor signalling in tongue cancer and its potential role in oral carcinogenesis - a short report

“…Tissue sections (5 μm) that were obtained from OED and OTSCC patients and from healthy controls, were treated as described in our recent study [26]. The slides were incubated overnight in 1) 1 μg/ml rabbit anti-human polyclonal H 4 R antibody (LifeSpan Biosciences Inc., Seattle, WA, USA) and 1 μg/ml rabbit anti-human monoclonal mast cell tryptase antibody (Abcam, Cambridge, UK) at +4°C; 2) biotin-conjugated secondary antibodies (Vector Laboratories; 1:200) for 1 h; 3) avidin-biotinperoxidase complex (Vector Laboratories; 1:200) for 1 h; 4) diaminobenzidine tetrahydrochloride for 10 min.…”

The effect of smoking on clinical presentation and expression of TLR-2 and CD34 in Oral lichen Planus patients: clinical and immunohistochemical study

“…This is in accordance to Ohno et al [8] who revealed high expression in basal keratinocytes of the normal buccal mucosa. This finding could be explained by Salem et al [25] who pointed out that the outmost epithelial layers depend on their junctional attachments for defense not needing to express TLRs whereas the deeper basal cells use their TLRs to provide immunologic backup.…”