Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-kappaB activation.
Fine particles in the air have been associated with increased mortality and morbidity. Particulate air pollution is a complex mixture which varies by region and includes a number of components including residual oil fly ash (ROFA), a byproduct of power plant and industry fuel-oil combustion. Human airway epithelial cells exposed to ROFA release inflammatory cytokines including interleukin (IL)-6, IL-8, and tumor necrosis factor. Expression of these genes is dependent upon pretranscriptional binding of cis regulatory elements, including nuclear factor kappaB (NF-kappaB). To investigate the role of NF-kappaB in the particulate-induced IL-6 response, we exposed human airway epithelial cells (BEAS-2B) to ROFA in vitro. ROFA stimulated a time- and dose-dependent increase in IL-6 messenger RNA (mRNA), which was preceded by the activation of nuclear proteins binding to the NF-kappaB sequence motif in the IL-6 promoter. Transient transfection of BEAS-2B cells with the 5' promoter region of the IL-6 gene linked to a luciferase reporter gene confirmed that NF-kappaB binding is necessary for the transcription of IL-6 mRNA. The IL-6 response was inhibited by the metal chelator deferoxamine and the free radical scavenger N-acetyl-L-cysteine, suggesting that the activation of NF-kappaB may be mediated through reactive oxygen intermediates generated by transition metals found in ROFA. Activation of NF-kappaB may therefore be a critical first step in the inflammatory cascade following exposure to particles generated by oil combustion.
Quay
J L
JL
National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Reed
W
W
Samet
J
J
Devlin
R B
RB
D000111:Acetylcysteine / Q000494:pharmacology; D000393:Air Pollutants / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002244:Carbon / Q000633:toxicity; D002460:Cell Line; D060729:Coal Ash; D004247:DNA / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005648:Fuel Oils; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008670:Metals / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism*; D052638:Particulate Matter; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000393:Air Pollutants; D060729:Coal Ash; D016166:Free Radical Scavengers; D005648:Fuel Oils; D015850:Interleukin-6; D008670:Metals; D016328:NF-kappa B; D052638:Particulate Matter; D012333:RNA, Messenger; D002244:Carbon; D004247:DNA; D003676:Deferoxamine; D000111:Acetylcysteine