Background: Airway inflammation and excessive mucin production are pathophysiological characteristics of airway diseases.Fipronil, a pesticide, is being extensively used in agriculture and veterinary medicine worldwide. However, this compound impairs immune function in non-target organisms. The present study aimed to evaluate the effect of fipronil on pro-inflammatory cytokine and mucus production and signalling pathways in human primary nasal epithelial cells.
Methodology:The effect of fipronil on pro-inflammatory cytokine and MUC5AC expression and the signalling pathway of fipronil were investigated using real-time PCR, enzyme immunoassays, immunofluorescence, and immunoblot analysis with specific inhibitors and small interfering RNA.Results: Fipronil treatment increased pro-inflammatory cytokine interleukin (IL)-1β, IL-6, IL-8, and MUC5AC expression in human primary nasal epithelial cells. It also induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mitogenactivated protein kinase (MAPK), p38 MAPK, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). MAPK and NF-kB inhibitor treatment significantly inhibited increases in IL-1β, IL-6, IL-8, and MUC5AC expression. Ex vivo data confirmed that fipronil-induced MUC5AC expression occurs through ERK1/2, p38, and NF-κB signalling pathways in nasal inferior turbinate tissue.Conclusions: Fipronil induced pro-inflammatory cytokine IL-1β, IL-6, IL-8, and MUC5AC expression via ERK1/2 MAPK, p38 MAPK, and NF-κB in human primary nasal epithelial cells.