PMID- 31680128 OWN - NLM STAT- MEDLINE DCOM- 20200720 LR - 20200720 IS - 0300-0729 (Print) IS - 0300-0729 (Linking) VI - 58 IP - 1 DP - 2020 Feb 1 TI - Fipronil upregulates inflammatory cytokines and MUC5AC expression in human nasal epithelial cells. PG - 66-73 LID - 10.4193/Rhin19.172 [doi] AB - 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. FAU - Kwak, S AU - Kwak S AD - Department of Medical Science, College of Medicine, Graduate School of Yeungnam University, Daegu, Republic of Korea; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea. FAU - Choi, Y S AU - Choi YS AD - Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea. FAU - Na, H G AU - Na HG AD - Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea. FAU - Bae, C H AU - Bae CH AD - Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea. FAU - Song, S-Y AU - Song SY AD - Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea. FAU - Kim, Y-D AU - Kim YD AD - Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of Korea. LA - eng PT - Journal Article PL - Netherlands TA - Rhinology JT - Rhinology JID - 0347242 RN - 0 (Cytokines) RN - 0 (MUC5AC protein, human) RN - 0 (Mucin 5AC) RN - 0 (NF-kappa B) RN - 0 (Pyrazoles) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - QGH063955F (fipronil) SB - IM MH - Cells, Cultured MH - Cytokines/*metabolism MH - Epithelial Cells/*drug effects/metabolism MH - Humans MH - Mucin 5AC/*metabolism MH - NF-kappa B/metabolism MH - Pyrazoles/*pharmacology MH - Signal Transduction MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2019/11/05 06:00 MHDA- 2020/07/21 06:00 CRDT- 2019/11/05 06:00 PHST- 2019/11/05 06:00 [pubmed] PHST- 2020/07/21 06:00 [medline] PHST- 2019/11/05 06:00 [entrez] AID - 2192 [pii] AID - 10.4193/Rhin19.172 [doi] PST - ppublish SO - Rhinology. 2020 Feb 1;58(1):66-73. doi: 10.4193/Rhin19.172.