Psoralen inhibits the inflammatory response and mucus production in allergic rhinitis by inhibiting the activator protein1 pathway and the downstream expression of cystatin‑SN.

Abstract

Psoralen (PSO) exerts anti-inflammatory pharmacological effects and plays an important role in a variety of inflammatory diseases. However, the effects of PSO with allergic rhinitis (AR) are yet to be reported. In the present study, an in vitro AR model was generated by inducing JME/CF15 human nasal epithelial cells with IL-13, after which MTT was used to assess the cytotoxicity of PSO. The expression levels of inflammatory cytokines (granulocyte-macrophage colony-stimulating factor and Eotaxin) were determined by ELISA. Furthermore, the expression of inflammatory IL-6 and −8, as well as mucin 5AC, was assessed by reverse transcription-quantitative PCR and western blotting, and cellular reactive oxygen species were detected using a 2′,7′-dichlorodihydrofluorescein diacetate fluorescent probe. Western blotting was also used to detect the expression and phosphorylation of c-Fos and c-Jun in the activator protein 1 (AP-1) pathway, as well as the expression of cystatin-SN (CST1). PSO inhibited the inflammatory response and mucus production in IL-13-induced JME/CF15 cells. Furthermore, the levels of c-Fos and c-Jun phosphorylation in the AP-1 pathway were decreased in IL-13-induced JME/CF15 cells following PSO treatment. The expression of pathway proteins was activated by the addition of PMA, an AP-1 pathway activator, which concurrently reversed the inhibitory effects of PSO on the inflammatory response and mucus formation. The addition of an AP-1 inhibitor (SP600125) further inhibited pathway activity, and IL-13-induced inflammation and mucus formation was restored. In conclusion, PSO regulates the expression of CST1 by inhibiting the AP-1 pathway, thus suppressing the IL-13-induced inflammatory response and mucus production in nasal mucosal epithelial cells.