Prolonged poly(ADP-ribose) polymerase-1 activity regulates JP-8-induced sustained cytokine expression in alveolar macrophages.
Environmental pollutants inducing oxidative stress stimulate chronic inflammatory responses in the lung leading to pulmonary tissue dysfunction. In response to oxidative stress, alveolar macrophages produce both reactive oxygen species and reactive nitrogen species, which induce the expression of a wide variety of immune-response genes. We found that a prolonged exposure of alveolar macrophages to a nonlethal dose (8 microg/ml) of JP-8, the kerosene-based hydrocarbon jet fuel, induced the persistent expression of IL-1, iNOS, and COX-2, as well as cell adhesion molecules (ICAM-1 and VCAM-1). Because poly(ADP-ribose) polymerase (PARP-1), a coactivator of NF-kappaB, regulates inflammatory responses and associated disorders in the airways, we determined whether JP-8 induces the poly(ADP-ribosyl)ation automodification of PARP-1 in alveolar macrophages. We observed that PARP-1 is activated in a time-dependent manner, which was temporally coincident with the prolonged activation of NF-kappaB and with the augmented expression of the proinflammatory factors described above. The 4 microg/ml dilution of JP-8 also increased the activity of PARP-1 as well as the expression of iNOS and COX-2, indicating that lower doses of JP-8 also affect the regulation of proinflammatory factors in pulmonary macrophages. Together, these results demonstrate that an extensive induction of PARP-1 might coordinate the persistent expression of proinflammatory mediators in alveolar macrophages activated by aromatic hydrocarbons that can result in lung injury from occupational exposure.
Espinoza
Luis A
LA
Department of Biochemistry and Molecular Biology & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA. lae2@georgetown.edu
Smulson
Mark E
ME
Chen
Zun
Z
D000818:Animals; D002460:Cell Line; D003470:Culture Media; D016207:Cytokines / Q000235:genetics*; D004785:Environmental Pollutants; D005579:Fossil Fuels / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006838:Hydrocarbons / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000502:physiology*; D023421:Models, Animal; D016273:Occupational Exposure; D030421:Peroxynitrous Acid / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003470:Culture Media; D016207:Cytokines; D004785:Environmental Pollutants; D005579:Fossil Fuels; D006838:Hydrocarbons; C098607:JP8 aviation fuel; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D011065:Poly(ADP-ribose) Polymerases; D005978:Glutathione