Arctigenin relieves inflammation and remodels the nasal epithelial barrier function in allergic rhinitis via the KLF5/BIRC3/NFκB axis

Allergic rhinitis (AR) is a significant global health issue that necessitates effective treatments. This paper investigates the mechanism of arctigenin (ATG) in alleviating AR. An AR mouse model was constructed and administered with different doses of ATG or positive control dexamethasone. Human nasal epithelial cells (HNEpCs) were stimulated with IL-4 and IL-13 to mimic AR-induced epithelial cell damage. Bioinformatic analysis was performed to predict target proteins of ATG and downstream factors of KLF5. AR mice and HNEpCs were treated with KLF5 overexpression lentivirus and BIRC3 knockdown lentivirus. HNEpCs were treated with NF-κB pathway agonist TWEAK. Our results revealed that ATG remodeled the nasal epithelial barrier function and alleviated inflammation in AR mice and inhibited IL-4/IL-13-induced inflammatory injury in HNEpCs. Mechanistically, ATG inhibited the expression of KLF5 protein. KLF5 transcriptionally activated BIRC3 and the NF-κB pathway. KLF5 overexpression exacerbated inflammatory injury in AR mice and HNEpCs, which was reversed by BIRC3 knockdown. NF-κB pathway agonist exacerbated inflammatory injury in HNEpCs. In conclusion, ATG remodels the nasal epithelial barrier function and alleviates AR in mice by inhibiting KLF5 protein expression and BIRC3 transcription and impairing the NF-κB pathway.

Allergic rhinitis; Arctigenin; BIRC3; KLF5; Nasal epithelial barrier function.