GLP-1通过JAK-STAT3通路减轻口腔扁平苔藓中的炎症和氧化应激

Abstract

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease with immune-mediated pathogenesis and potential for malignant transformation. Elevated inflammatory cytokines and oxidative stress contribute to its progression. This study explored the therapeutic potential of glucagon-like peptide-1 (GLP-1) in modulating inflammation and oxidative stress in OLP. To establish an in vitro OLP model, human oral keratinocytes (HOK) were treated with lipopolysaccharide (LPS) at varying concentrations, and 5 µg/ml was selected as the optimal concentration based on CCK-8 assay results. The inflammatory response was assessed using qRT-PCR and ELISA to measure IL-6, TNF-α, and IL-1β expression. Oxidative stress levels were determined using DCF-DA fluorescence staining for ROS detection and SOD activity assays. The involvement of the JAK/STAT3 pathway was evaluated using western blot analysis of JAK, p-JAK, STAT3, and p-STAT3 protein expression. The OLP model was successfully established in HOK cells using LPS, with significant morphological changes and reduced cell viability observed at 10 µg/ml and higher concentrations. LPS stimulation induced inflammation and oxidative stress, marked by elevated IL-6, TNF-α, IL-1β mRNA and protein levels, increased ROS production, and reduced SOD activity. GLP-1 treatment (10 nM to 100 nM) significantly reduced inflammation and oxidative stress in a dose-dependent manner. GLP-1 inhibited the expression of pro-inflammatory cytokines and decreased ROS levels while enhancing SOD activity. Further analysis revealed that GLP-1’s effects were mediated through the JAK/STAT3 pathway, as demonstrated by the suppression of JAK and STAT3 phosphorylation, which was comparable to the effects of the JAK/STAT3 inhibitor Stattic. This study elucidated that GLP-1 mitigated inflammation and oxidative stress in an in vitro model of OLP via JAK/STAT3 signaling pathway, demonstrating its potential as a therapeutic agent in OLP. Graphcial Glucagon-like