This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Interaction of Lung Cells with Ozone and Particulate MatterExposure to DEP has been implicated in lung inflammation, and exacerbation of asthma and chronic obstructive pulmonary disease. The cellular events leading to DEP-induced effect in the lung remain unknown. Polycyclic aromatic hydrocarbons (PAHs) adsorbed on DEP are major constituents of DEP, and their role in DEP-induced effect in the lung, also remains to be elucidated. Exposure to PAHs has been shown to induce apoptosis in alveolar macrophages. We report here that exposure of the alveolar macrophage cell line, RAW 264.7 to DEP (250 ug/ml x 4 hr) induces significant synthesis of TNF-alpha protein (303 plus/minus 44 pg/ml, n = 4, p less than 0.05) compared to control cultures (33 plus/minus 11 pg/ml, n = 8). DEP-induced TNF-alpha synthesis was significantly inhibited (86 plus/minus 9% inhibition, n = 4, p less than 0.05) in the presence of pyrene (20 uM x 4 hr). In addition, inhibition of NF-kappaB in DEP-exposed cultures resulted in a significant attenuation of TNF-alpha protein production, as demonstrated by NF-kappaB inhibitor (BAY11-7082) studies. Furthermore, pyrene and benzanthracene at concentrations of 20, 40, and 100 uM (x 48 hr) significantly enhanced DEP-induced apoptosis in RAW 264.7 cells in a dose-dependant manner (8 plus/minus 1%, n = 8, p less than 0.01, 31 plus/minus 2%, n = 8, p less than 0.01, and 59.5 plus/minus 3%, n = 8, p less than 0.01, respectively), as compared to control cultures and cultures treated with DEP alone or with a mixture of pyrene and benzanthracene alone. The results of the present study indicate that DEP activate alveolar macrophages by inducing the over-expression of TNF-alpha gene. Furthermore, PAHs commonly adsorbed on DEP surfaces may be responsible for the effect of DEP on apoptosis in alveolar macrophages by inhibiting NF-kappaB activation.
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