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. 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 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)-1beta, 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-kB). MAPK and NF-kB inhibitor treatment significantly inhibited increases in IL-1beta, IL-6, IL-8, and MUC5AC expression. Ex vivo data confirmed that fipronil-induced MUC5AC expression occurs through ERK1/2, p38, and NF-kB signalling pathways in nasal inferior turbinate tissue.

CONCLUSIONS

Fipronil induced pro-inflammatory cytokine IL-1beta, IL-6, IL-8, and MUC5AC expression via ERK1/2 MAPK, p38 MAPK, and NF-kB in human primary nasal epithelial cells.