Activation of transcription factor IL-6 (NF-IL-6) and nuclear factor-kappaB (NF-kappaB) by lipid ozonation products is crucial to interleukin-8 gene expression in human airway epithelial cells.
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 microM), increases the activity of phospholipase C, nuclear factors-kappaB (NF-kappaB), 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 microM x 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-kappaB and NF-IL-6. Transfection studies using luciferase reporter assays demonstrated that HHP-C9 induced a significant increase in NF-kappaB-DNA binding activity (37 +/- 7% increase over control, n = 6, P < 0.05). Inhibition of NF-kappaB 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-kappaB in regulating the expression of IL-8 in cultured human airway epithelial cells exposed to LOP, the biological products of ozone in the lung.
Kafoury
Ramzi M
RM
Center for Environmental Health, Jackson State University, Jackson, Mississippi, USA. ramzi.m.Kafoury@jsums.edu
Hernandez
Jazmir M
JM
Lasky
Joseph A
JA
Toscano
William A
WA
Friedman
Mitchell
M
D000473:Alkanes / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008055:Lipids; D016328:NF-kappa B / Q000096:biosynthesis*; D010083:Oxidants, Photochemical; D010126:Ozone; D010545:Peroxides / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000166:cytology
C405904:1-hydroxy-1-hydroperoxynonane; D000473:Alkanes; D022782:CCAAT-Enhancer-Binding Protein-beta; D016209:Interleukin-8; D008055:Lipids; D016328:NF-kappa B; D010083:Oxidants, Photochemical; D010545:Peroxides; D010126:Ozone; D004247:DNA