Activation In Vitro

High levels of ambient air pollution are associated with exacerbation of asthma and respiratory morbidity, yet little is known concerning the mechanisms of inflammation and toxicity by components of inhaled particulate matter (PM). Brief inhalation of PM 2.5 (particles of an aerodynamic diameter of , 2.5 microns) (300 m g/m 3 air for 6 h followed by a period of 24 h in clean air) by either C3H/HeJ or C57/BL6 mice caused significant ( P < 0.05) increases in steady-state messenger RNA (mRNA) levels of a number of nuclear factor (NF)k B–associated and/ or –regulated genes, including tumor necrosis factora and b , interleukin-6, interferong , and transforming growth factorb . Lung mRNA levels of lymphotoxinb and macrophage migration inhibitory factor were unchanged. In murine C10 alveolar cells and an NFk B–luciferase reporter cell line, exposure to PM 2.5 at noncytotoxic concentrations resulted in increases in transcriptional activation of NFk B–dependent gene expression which were inhibited in the presence of catalase. Early and persistent increases in intracellular oxidants, as measured by flow cytometry and cell imaging using the oxidant probe 2 9 7 9 -dichlorofluoroscin diacetate, were observed in epithelial cells exposed to PM 2.5 and ultrafine carbon black particles. Studies here are the first to show NFk B–related inflammatory and cytokine gene expression after inhalation of PM 2.5 and oxidant-dependent induction of NFk B activity by PM 2.5 in pulmonary epithelial cells.