Expression of JP-8-induced inflammatory genes in AEII cells is mediated by NF-kappaB and PARP-1.
Lung epithelial cells are critical in the regulation of airway inflammation in response to environmental pollutants. Altered activation of NF-kappaB 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 microg/ml) of the jet fuel JP-8 induces in a rat alveolar epithelial cell line (RLE-6TN) a prolonged activation of NF-kappaB as well as the increased expression of the proinflammatory cytokines TNF-alpha and IL-8, which are regulated by NF-kappaB. 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-alpha, IL-8, and IL-6, confirming the in vitro data. The poly(ADP-ribosyl)ation of PARP-1, a coactivator of NF-kappaB, was coincident with the prolonged activation of NF-kappaB 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.
Espinoza
Luis A
LA
Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC 20057, USA.
Tenzin
Fnu
F
Cecchi
Andrea O
AO
Chen
Zun
Z
Witten
Mark L
ML
Smulson
Mark E
ME
D000336:Aerosols; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D015870:Gene Expression; D006838:Hydrocarbons / Q000009:adverse effects*; D020672:I-kappa B Proteins; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress; D010766:Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism* / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000336:Aerosols; D006838:Hydrocarbons; D020672:I-kappa B Proteins; D015850:Interleukin-6; C098607:JP8 aviation fuel; D016328:NF-kappa B; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases