Paeoniflorin Upregulates β-Defensin-2 Expression in Human Bronchial Epithelial Cell Through the p38 MAPK, ERK, and NF-κB Signaling Pathways

Paeoniflorin (PF) is one of the principal components of peony, a plant widely used in traditional Chinese medicine for its anti-inflammatory and immunomodulatory effects. Human β-defensin-2 (hBD-2) is an antimicrobial peptide that acts as the first line of defense against bacterial, viral, and fungal infections. This study aims to determine whether or not PF can regulate the expression of hBD-2 and its possible molecular mechanism in human bronchial epithelial cells (HBECs). Real-time quantitative reverse transcription PCR showed that PF can enhance the mRNA expression level of hBD-2 in a concentration- and time-dependent manner in HBECs. Further studies demonstrated that the mRNA and protein expression levels of hBD-2 were attenuated by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, the extracellular signal-regulated kinase (ERK) inhibitor PD98059, and the nuclear factor kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate (PDTC)). The phosphorylation of p38 MAPK, ERK, and c-Jun N-terminal kinase was detected by Western blot analysis, and the NF-κB translocation of 16HBECs after PF treatment was analyzed by immunofluorescence. These results support that PF upregulates hBD-2 expression in HBECs through the p38 MAPK, ERK, and NF-κB signaling pathways. These findings provide a new pharmacological mechanism of PF for the treatment of microbial infections by strengthening epithelial antimicrobial barriers.