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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
Author(s) -
Kafoury Ramzi M.,
Hernandez Jazmir M.,
Lasky Joseph A.,
Toscano William A.,
Friedman Mitchell
Publication year - 2007
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.20246
Subject(s) - chemistry , transcription factor , interleukin , nf κb , microbiology and biotechnology , reporter gene , interleukin 8 , gene expression , biochemistry , biology , signal transduction , inflammation , immunology , cytokine , gene
Ozone (O 3 ) is a major component of smog and an inhaled toxicant to the lung. O 3 rapidly reacts with the airway epithelial cell membrane phospholipids to generate lipid ozonation products (LOP). 1‐Hydroxy‐1‐hydroperoxynonane (HHP‐C9) is an important LOP, produced from the ozonation of 1‐palmitoyl‐2‐oleoyl‐sn‐glycerol‐3‐phosphatidylcholine. This LOP, at a biologically relevant concentration (100 μM), increases the activity of phospholipase C, nuclear factors‐κB (NF‐κB), and interleukin‐6 (NF‐IL‐6) and the expression of the inflammatory gene, interleukin‐8 (IL‐8) in a cultured human bronchial epithelial cell line (BEAS‐2B). The signaling pathways of ozone and its biologically‐active products are as yet undefined. In the present study, we report that the HHP LOP, HHP‐C9 (100 μM × 4 h), activated the expression of IL‐8 (218 ± 26% increase over control, n = 4, P < 0.01) through an apparent interaction between the two transcription factors, NF‐κB and NF‐IL‐6. Transfection studies using luciferase reporter assays demonstrated that HHP‐C9 induced a significant increase in NF‐κB‐DNA binding activity (37 ± 7% increase over control, n = 6, P < 0.05). Inhibition of NF‐κB showed a statistically significant but modest decrease in IL‐8 release, which suggested a role for another transcription factor, NF‐IL‐6. Exposure of BEAS‐2B cells to HHP‐C9 induced a significant increase in the DNA binding activity of NF‐IL‐6 (45 ± 11% increase over control, n = 6, P < 0.05). The results of the present study indicate that NF‐IL‐6 interacts with NF‐κB in regulating the expression of IL‐8 in cultured human airway epithelial cells exposed to LOP, the biological products of ozone in the lung. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 159–168, 2007.