Bisphenol A and F exposure suppresses MMP9 to drive nasal epithelial inflammation and senescence: a protective target for allergic rhinitis.

Allergic rhinitis (AR) is a prevalent inflammatory disorder of the upper airways, and exposure to environmental endocrine-disrupting chemicals such as bisphenol A (BPA) and bisphenol F (BPF) has been implicated in its pathogenesis, yet the underlying molecular mechanisms remain poorly understood. We integrated network toxicology, bioinformatics, and machine learning approaches to identify key target genes linking BPA/BPF exposure to AR, followed by molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) to evaluate binding affinities. In vitro experiments using human nasal epithelial cells (HNEpC) were conducted to validate the effects of BPA/BPF on cell viability, apoptosis, inflammatory cytokines, senescence-associated secretory phenotype (SASP), and the NF-κB signaling pathway, with further functional assessment via MMP9 overexpression. Four common genes (MAPT, MMP9, CHRM3, ESR2) were identified for BPA and three (MMP9, CHRM3, ESR2) for BPF. SPR confirmed direct binding of both bisphenols to MMP9 with KD values of 3.46 μM (BPA) and 9.47 μM (BPF). BPA/BPF treatment inhibited cell viability, suppressed MMP9, promoted apoptosis, upregulated IL-4, IL-6, IL-8, IL-13, CCL2, TNF-α, and IL-1β, downregulated MMP1, and suppressed the NF-κB pathway. MMP9 overexpression reversed these effects. Our findings demonstrate that BPA and BPF promote AR pathogenesis through MMP9 suppression, SASP activation, and NF-κB inhibition, identifying MMP9 as a potential therapeutic target for pollutant-exacerbated AR.