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DIESEL EXHAUST PARTICLE-INDUCED EPITHELIAL TOXICITY IS MODULATED BY UV-IRRADIATION
MANZO, N., J. E. RICHARDS, R. SLADE, L. D. MARTIN, AND J. A. DYE. DIESEL EXHAUST PARTICLE-INDUCED EPITHELIAL TOXICITY IS MODULATED BY UV-IRRADIATION. Presented at American Thoracic Society Annual Meeting, San Francisco, CA, May 18 - 23, 2007.
Asthma is a chronic inflammatory disorder of the airways affecting nearly 20 million individuals in the U.S alone. Asthmatic symptoms can be exacerbated by environmental insults like exposure to particulate matter (PM). Diesel exhaust particles (DEP) account for a significant portion of PM. Interactions of DEP with ultraviolet radiation can chemically or physically transform its surface reactivity.
We hypothesized that airway epithelial exposure to UV-irradiated DEP would result in greater cell injury as compared to non-UV irradiated DEP. Primary mouse tracheal epithelial cells (MTE) grown at an air-liquid interface (ALI) were used to model a healthy airway epithelium. These cells were exposed to vehicle, 200µg/cm2 of DEP, or 200µg/cm2 of UV-DEP for 24hrs. Supernatants (apical and basal) and cell lysates were collected at 24 and 48hrs. The degree of injury was inferred by the release of lactate dehydrogenase. Cellular antioxidant responses were determined using HPLC to measure intracellular GSH vs GSSG content. Quantification of MIP-2 and RANTES by ELISA was used to assess inflammatory responses.
We observed no substantial cell injury, protein leakage, or change in antioxidant status when the epithelial cells were exposed to 200µg/cm2 DEP for 24 or 48hrs as compared to vehicle treatment alone. However, UV-irradiated DEP induced mild cytotoxicity, increased apical protein accumulation, as well as an increased intracellular GSH levels. A decrease in RANTES release, and not MIP-2, was observed in cells treated with either DEP treatment.
In conclusion, healthy primary MTE cells under ALI conditions were able to tolerate a high dose of DEP, seemingly through effective antioxidant responses. UV-irradiated DEP induced a still greater antioxidant response. In diseased airways, however, such exposures may likely modulate redox sensitive inflammatory mediators.
*This abstract does not represent US EPA policy*
Funded by the NCSU/EPA Co-Op Training Program (CT826512010)
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
EXPERIMENTAL TOXICOLOGY DIVISION
PULMONARY TOXICOLOGY BRANCH