Ursodeoxycholic acid ameliorates particulate matter-induced cutaneous inflammation via the AhR/ERK signaling pathway.

Particulate matter (PM) and its constituent polycyclic aromatic hydrocarbons (PAHs) are major environmental hazards that induce skin inflammation by activating the aryl hydrocarbon receptor (AhR) and its downstream mitogen-activated protein kinase (MAPK) signaling pathways. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid, originally identified in bear bile, and has been used for the treatment of cholesterol gallstones and primary biliary cholangitis. Although recent pharmacological studies have highlighted its roles in metabolic and autoimmune diseases, its specific effect on the PM-induced cutaneous inflammatory environment remains unclear. Therefore, this study aimed to investigate the protective effects and underlying mechanisms of UDCA against PM-induced AhR-activated skin immune dysregulation. Human keratinocytes were stimulated with PM and tumor necrosis factor-α/interferon-γ to analyze AhR translocation and inflammatory cytokine production. Mice exhibiting skin immune abnormalities were generated by exposure to PM after application of 2,4-dinitrochlorobenzene. Subsequently, clinical severity, histopathological changes, and the MAPK signaling pathway were assessed to evaluate overall pathological and tissue-level responses. In vitro, UDCA significantly inhibited PM-induced nuclear translocation of AhR and decreased interleukin (IL)-6 and IL-4 production, though it upregulated GM-CSF, IL-1β, and IL-8 levels. In vivo, UDCA significantly attenuated the PM-exacerbated SCORAD index, scratching behavior, transepidermal water loss, and serum immunoglobulin E. Furthermore, UDCA reduced epidermal thickness, suppressed eosinophil and mast cell infiltration, and inhibited ERK phosphorylation in skin tissues. These findings indicate that UDCA ameliorates PM-induced skin immune dysregulation by modulating the AhR and ERK signaling pathways.