Submitted on February 6, 2006
Revised on May 11, 2006
Expression of JP-8-induced Inflammatory Genes in AEII Cells is Mediated by NF-
B and PARP-1
Luis A Espinoza1, Fnu Tenzin1, Andrea O Cecchi1, Mark L Witten2, and Mark E Smulson1*
1 Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC, USA,
2 Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, The University of Arizona Health Sciences Center, Tucson, AZ, USA
* To whom correspondence should be addressed. 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 pro-inflammatory 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 pro-inflammatory 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 pro-inflammatory 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.
