ABSTRACT: Nickel induces IL-8 expression in human airway epithelial cells.

Inhalation of nickel subsulfide by humans and rodents has been linked to chronic active inflammation and fibrosis of the lungs. However the mechanisms for these effects are not well understood. Therefore, cell culture experiments using BEAS 2B human airway epithelieal cells were conducted to test the hypothesis that exposure to non-cytotoxic levels of nickel induce expression of cytokines, such as IL-8, which is known to contribute to both inflammatory and fibrotic disease. IL-8 MRNA levels were significantly increased following 16 to 24 hour exposures to 2.34 mg nickel/cm2 of culture surface. Message stability studies with the transcriptional inhibitor actinomycin D demonstrated that IL-8 mRNA was not stabilized following a 16 hour exposure to nickel. Transient transfection of the full-length IL-8 promoter linked to the lucierase gene demonstrated chronic trancsriptional activation for 48 hours following exposure of the cells to nickel. Truncation contructs of the IL-8 promoter demonstrated that nickel-induced IL-8 gene transcription required a region of the promoter between -272 and -133 bp from the transcriptional tart site. These studies also demonstrated that the -133 bp promoter construct, containing cytokine and hypoxia-sensitive AP-1, NFIL-6 and NF-kB cis-elements, was not chronically induced by nickel. Further analysis of the -272 to -133 bp region should identify transcriptional factors responsible for induction of IL-8 gene transcription by nickel. Supported by SBRP grant ES07373.

Soucy NV, Andrew AS, Barchowsky A. Nickel induces IL-8 expression in human airway epithelial cells. The Toxicologist 60:317, 2001.