Am. J. Respir. Cell Mol. Biol., Volume 19, Number 1, July, 1998 98-106

Air Pollution Particles Induce IL-6 Gene Expression in Human Airway Epithelial Cells via NF-B Activation

Jacqueline L. Quay, William Reed, James Samet, and Robert B. Devlin

National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park; and Center for Environmental Medicine and Lung Biology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

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 B (NF-B). To investigate the role of NF-B 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-B 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-B 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-B may be mediated through reactive oxygen intermediates generated by transition metals found in ROFA. Activation of NF-B may therefore be a critical first step in the inflammatory cascade following exposure to particles generated by oil combustion.

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