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PARP‐1 activation mediates expression of NF‐κB‐regulated pro‐inflammatory mediators in response to JP‐8 jet fuel in alveolar macrophages
Author(s) -
Espinoza Luis A.,
Smulson Mark E
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1169-c
Subject(s) - microbiology and biotechnology , inflammation , chemistry , reactive oxygen species , alveolar macrophage , nf κb , oxidative stress , reactive nitrogen species , immunology , macrophage , cancer research , biology , in vitro , biochemistry
Lung alveolar macrophages are critical in the regulation of airway inflammation in response to environmental pollutants. In response to oxidative stress, macrophages produce both reactive oxygen species (ROS) and nitrogen species (RNS), which induce the expression of a wide variety of immune‐response genes. We found that a prolonged exposure of rat alveolar macrophages to a non‐lethal dose (8 μg/ml) of JP‐8 (a hydrocarbon mix) during several time courses induced the persistent expression of IL‐1, iNOS, COX‐2, as well as cell adhesion molecules (ICAM‐1 and VCAM‐1). We determined that JP‐8 induced the poly(ADP‐ribosyl)ation automodification of PARP‐1, a coactivator of NF‐κB, in alveolar macrophages. PARP‐1 is activated in a time dependent manner, which was temporally coincident with the prolonged activation of NF‐κB, and with the augmented expression of the pro‐inflammatory factors described above. Together, these results demonstrated that an extensive induction of PARP‐1 might coordinate the persistent expression pro‐inflammatory mediators in alveolar macrophages activated by aromatic hydrocarbons that can result in lung injury of occupational exposure. Supported by the AFOSR Grant FA9550‐04‐1‐0395.