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The Involvement of Superoxide and Nitric Oxide in Inflammation-Enhanced Diesel Exhaust Particle Cytotoxicity
Citation:
MANZO, N., J. E. RICHARDS, R. SLADE, J. M. LAW, AND J. A. DYE. The Involvement of Superoxide and Nitric Oxide in Inflammation-Enhanced Diesel Exhaust Particle Cytotoxicity. Presented at North Carolina State University Graduate Student Research Symposium, Raleigh, NC, March 18, 2009.
Impact/Purpose:
Information on Nitric Oxide collaboration in inflamation enhanced diesel exhaust particle induced injury.
Description:
Thirty-four million Americans have asthma, a chronic inflammatory lung disease. Although the mechanisms are unclear, epidemiologic studies show that exposure of asthmatics to air pollutants, like diesel exhaust particles (DEP), is more likely to result in adverse health effects. We have previously shown that in an analogous in vitro system that models “healthy” (control) and “inflamed” (asthmatic) epithelial cells, exposure of “inflamed” cells to DEP results in greater cell injury. To understand this enhanced cell injury, we investigated further the role of oxidative stress in the setting of inflammation. We hypothesized that “inflamed” epithelial cells exposed to DEP would result in oxidative stress, in part, due to the combined effect of decrease cytoprotective mechanisms and nitric oxide (NO) production. “Inflamed” LA-4 epithelial cells, induced by treatment with pro-inflammatory cytokines (TNFα+IL-1β+IFNγ), were exposed to DEP, and subsequently analyzed for reactive oxygen species (ROS) as measured by the fluorescent probe H2DCFDA, and superoxide dismutase (SOD) activity. Results indicate that intracellular ROS were significantly increased in “inflamed” cells exposed to DEP as compared to “inflamed” or DEP alone treated cells. To determine, if increased ROS was the result of decreased cytoprotective mechanism, the activity of SOD, an enzyme involved in superoxide anion catabolism, was measured and shown to be significantly reduced in “healthy” cells exposed to DEP. Lastly, NO, a free radical gas often induced in asthma, can interact with ROS to produce additional potent and long lived radicals. Using a NO inhibitor, L-NAME, ROS production was significantly decreased in DEP exposed “inflamed” cells. Together, exposure of “inflamed” cells to DEP can result in cellular oxidative stress, due to the combined decrease in antioxidant defenses and elevated NO. Similar mechanism may account for the adverse health effects experienced by asthmatics exposed to DEP. [Funded by EPA CT826512010; Abstract does not represent USEPA policy]