Activation of transcription factor IL‐6 (NF‐IL‐6) and nuclear factor‐κB (NF‐κB) by lipid ozonation products is crucial to interleukin‐8 gene expression in human airway epithelial cells

• DOI: 10.1002/tox.20246
• Publication Date: 2007-03-15T18:07:36Z
• Authors: Ramzi M. Kafoury; Jazmir M. Hernandez; Joseph A. Lasky; William A. Toscano; Mitchell Friedman
• Keywords: Interleukin 8

Abstract Ozone (O 3 ) is a major component of smog and an inhaled toxicant to the lung. O rapidly reacts with airway epithelial cell membrane phospholipids generate lipid ozonation products (LOP). 1‐Hydroxy‐1‐hydroperoxynonane (HHP‐C9) important LOP, produced from 1‐palmitoyl‐2‐oleoyl‐sn‐glycerol‐3‐phosphatidylcholine. This at biologically relevant concentration (100 μM), increases activity phospholipase C, nuclear factors‐κB (NF‐κB), interleukin‐6 (NF‐IL‐6) expression inflammatory gene, interleukin‐8 (IL‐8) in cultured human bronchial line (BEAS‐2B). The signaling pathways ozone its biologically‐active are as yet undefined. In present study, we report that HHP HHP‐C9 μM × 4 h), activated IL‐8 (218 ± 26% increase over control, n = 4, P < 0.01) through apparent interaction between two transcription factors, NF‐κB NF‐IL‐6. Transfection studies using luciferase reporter assays demonstrated induced significant NF‐κB‐DNA binding (37 7% 6, 0.05). Inhibition showed statistically but modest decrease release, which suggested role for another factor, Exposure BEAS‐2B cells DNA NF‐IL‐6 (45 11% results study indicate interacts regulating exposed biological © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 159–168, 2007.