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?

Abstract

High mobility group box 1 (HMGB1) is an extremely conserved DNA-binding protein that stabilizes nucleosomes and facilitates gene transcription in mammalian cells. When released extracellularly, HMGB1 becomes an alarmin that can mediate systemic diseases. High mobility group box 1 signals via two main receptors: receptor for advanced glycation end-products (RAGE) and toll-like receptor-4 (TLR4). We hypothesized that HMGB1 expression is increased in patients with oral lichen planus (OLP) relative to healthy controls. Therefore, HMGB1 and its receptors were mapped in tissue biopsies from 25 patients with OLP and from 20 healthy controls by immunostaining and ImageJ analysis. High mobility group box 1 was induced in oral keratinocytes in all patients with OLP. The band-like cell infiltrate in patients with OLP revealed very strong staining for RAGE. Likewise, TLR4 was overexpressed throughout OLP mucosa which co-localized with HMGB1. In conclusion, we suggest that OLP could partly be an HMGB1-mediated condition by creating a proinflammatory loop cycle via RAGE- and TLR4-signalling axes, which may contribute to the chronicity of this disease.

Keywords: HMGB1; OLP; RAGE; danger-associated molecular patterns; toll-like receptors.