Integrated network toxicology and transcriptomics analysis reveals the pathogenic mechanism linking volatile organic compounds exposure to rheumatoid arthritis.

Volatile organic compounds (VOCs), a significant category of air pollutants, have been linked to an elevated risk of rheumatoid arthritis (RA). However, their precise role in the pathogenesis and pathophysiology of RA remains poorly understood. This study aimed to elucidate the key mechanisms and targets through which VOCs contribute to RA. Potential targets related to both VOCs and RA were identified using STITCH, SwissTargetPrediction, SEA, GeneCards, and OMIM databases. Functional enrichment analysis was conducted with DAVID, while protein-protein interaction networks were constructed using STRING and Cytoscape to identify core targets. The dysregulation of these key targets was validated using a GEO dataset. Immune infiltration analysis was performed to evaluate correlations between VOC-affected core targets and immune cells. Molecular docking performed with CB-Dock2 confirmed binding affinities between VOC metabolites and core targets. Two common core targets, ICAM1 and CASP3, were identified as central to VOC-related effects in RA. VOCs may promote RA pathogenesis by engaging key mechanisms that include inflammatory signaling (TNF, IL-17, NF-κB), dysregulation of cellular processes (proteolysis, extracellular matrix disassembly), and altered immune responses (integrin-mediated leukocyte adhesion/migration and NK cell-mediated cytotoxicity). This study is the first to demonstrate that VOCs may promote the onset and progression of RA by modulating multiple signaling pathways and core target proteins, thereby altering immune-synovial cell interactions. These findings provide important theoretical insights for preventing and treating VOC-associated RA.