Fipronil upregulates inflammatory cytokines and MUC5AC expression in human nasal epithelial cells

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. How ever, 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)-1 beta, 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) mitogen-activated protein kinase (MAPIQ, p38 MAPK, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B). MAPK and NF-kappa B inhibitor treatment significantly inhibited increases in IL-1 beta, IL-6, IL-8, and MUC5AC expression. Ex vivo data confirmed that fipronil-induced MUC5AC expression occurs through ERK1/2, p38, and NF-kappa B signalling pathways in nasal inferior turbinate tissue. Conclusions: Fipronil induced pro-inflammatory cytokine IL-1 beta, IL-6, IL-8, and MUC5AC expression via ERK1/2 MAPK, p38 MAPK, and NF-kappa B in human primary nasal epithelial cells.