2025 Volume 50 Issue 1 Pages 11-21
A representative surfactant, benzalkonium chloride (BAC) is used as a disinfectant, but sometimes causes serious side effects, including lung disorders such as interstitial pneumonia. However, its pathogenic mechanisms remain unexplained. In this study, we identified a novel mechanism by which BAC initiates inflammatory responses that may be responsible for its side effects. We firstly investigated whether BAC initiates inflammation, and found that BAC promotes the secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β) but not tumor necrosis factor-α (TNF-α) in macrophages. Interestingly, the IL-1β secretion triggered by the surfactants was completely blocked by the K-ATP channel blocker glibenclamide or the calcium chelating agent 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM. Moreover, genetic experiments revealed that BAC-dependent IL-1β secretion is mediated by the NLRP3 inflammasome. These results suggest that derangement of ion fluxes associated with the interfacial effects of BAC triggers NLRP3 inflammasome activation and subsequent inflammation. Thus, the NLRP3-dependent mechanisms triggered by BAC may explain the pathogenesis of surfactant-caused adverse effects.
