This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0059OCv1 35/4/479    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Espinoza, L. A. Articles by Smulson, M. E. Search for Related Content PubMed PubMed Citation Articles by Espinoza, L. A. Articles by Smulson, M. E.

Expression of JP-8–Induced Inflammatory Genes in AEII Cells Is Mediated by NF-B and PARP-1

Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC; and Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, The University of Arizona Health Sciences Center, Tucson, Arizona

Correspondence and requests for reprints should be addressed to Dr. Mark E. Smulson, Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC 20057. E-mail: smulson{at}georgetown.edu

Lung epithelial cells are critical in the regulation of airway inflammation in response to environmental pollutants. Altered activation of NF-B is associated with expression of several proinflammatory factors in respiratory epithelial cells in response to an insult. Here we show that a low threshold dose (8 µg/ml) of the jet fuel JP-8 induces in a rat alveolar epithelial cell line (RLE-6TN) a prolonged activation of NF-B as well as the increased expression of the proinflammatory cytokines TNF- and IL-8, which are regulated by NF-B. The up-regulation of IL-6 mRNA in cells exposed to JP-8 appears to be a reaction of RLE-6TN cells to reduce the enhancement of proinflammatory mediators in response to the fuel. Moreover, lung tissues from rats exposed to occupational levels of JP-8 by nasal aerosol also showed dysregulated expression of TNF-, IL-8, and IL-6, confirming the in vitro data. The poly(ADP-ribosyl)ation of PARP-1, a coactivator of NF-B, was coincident with the prolonged activation of NF-B during JP-8 treatment. These results evidenced that a persistent exposure of the airway epithelium to aromatic hydrocarbons may have deleterious effects on pulmonary function.

Key Words: epithelial cells • inflammation • JP-8 jet fuel • NF-B • PARP-1