Abstract
The distinctive clinicopathologic characteristics of OLP indicated that both microbial dysbiosis and neurogenic inflammation may be jointly involved in its progression, and transient receptor potential vanilloid receptor-1 (TRPV1) may be a crucial element. The purpose of this study was to explore how TRPV1 mediated P. melaninogenica-induced inflammation. Meanwhile, we aimed to unravel how IL-36γ dysregulated the barrier function in oral keratinocytes. Here, the expression of TRPV1, calcitonin gene-related peptide (CGRP), and its receptor receptor activity-modifying protein 1 (RAMP1) in OLP patients were detected. Prevotella melaninogenica (P. melaninogenica) was used to build a mouse model of oral chronic inflammation. Normal human oral keratinocytes (NHOKs) stimulated by P. melaninogenica were used to examine TRPV1 activation and CGRP release. To investigate the effect of exogenous CGRP on Interleukin-36 gamma (IL-36γ) expression in NHOKs and bacterial viability, P. melaninogenica and NHOKs were treated with it, respectively. Recombinant IL-36γ protein was used to probe its regulation of oral epithelial barrier function. TRPV1, CGRP, and RAMP1 were substantially expressed in OLP. P. melaninogenica increased TRPV1 expression in mice and caused the release of CGRP and an increase in pro-inflammatory cytokines via activating TRPV1 in NHOKs. Blockade of TRPV1 suppressed P. melaninogenica-induced inflammation. CGRP boosted the production of IL-36γ released by NHOKs, resulting in lower expression of zonula occludens-1 (ZO-1). Also, CGRP can decrease the viability of P. melaninogenica. Together, these findings provide fresh insight into the vital role performed by P. melaninogenica-induced functional changes in oral epithelial cells and neurons in an intricate OLP inflammatory process.