# Epinephrine as a potential driver of oral lichen planus pathogenesis

## TL;DR

Stress-related epinephrine may worsen oral lichen planus by causing cell damage and inflammation.

## Contribution

This study identifies epinephrine as a novel driver of oral lichen planus through oxidative stress and immune activation.

## Key findings

- High epinephrine levels cause cytotoxicity in oral keratinocytes and DNA damage.
- Epinephrine reduces antioxidant proteins SOD2 and SESN2, increasing oxidative stress.
- Epinephrine activates STAT3 signaling and increases DAMPs like HMGB1 and ATP.

## Abstract

Oral lichen planus (OLP) is a chronic inflammatory condition characterized by CD8+ T cell-mediated apoptosis of oral epithelial cells. While psychological stress has been implicated in OLP pathogenesis, the underlying mechanisms remain unclear. This study explores the role of epinephrine, a primary stress-related catecholamine, in OLP progression. We found that high concentrations of epinephrine induce cytotoxicity in oral keratinocytes, marked by reduced cell viability and increased DNA damage. High-dose epinephrine also elevates oxidative stress by downregulating antioxidant proteins SOD2 and SESN2. Additionally, it activates the STAT3 signaling pathway through both alpha- and beta-adrenergic receptors. Furthermore, epinephrine increases levels of HMGB1 and extracellular ATP, key damage-associated molecular patterns (DAMPs) that could perpetuate chronic inflammation in OLP. These findings suggest that stress-induced epinephrine may exacerbate OLP by promoting oxidative stress, epithelial damage, and immune activation. Given the increased vascularization in OLP lesions, epinephrine’s effects may be amplified in affected tissues. Understanding the link between stress and OLP pathogenesis could provide new therapeutic targets for managing this condition.