Ultrafine airborne particles cause increases in protooncogene expression and proliferation in alveolar epithelial cells

Exposure to ambient particulate matter (PM) is linked to increases in respiratory morbidity and exacerbation of cardiopulmonary diseases. However, the important components of PM and their mechanisms of action in lung disease are unclear. We demonstrate the development of dose-related proliferation and apoptosis after exposure of an alveolar epithelial cell line (C10) to PM or to ultrafine carbon black (ufCB), a component of PM. Ribonuclease protection assays demonstrated that increases in mRNA levels of the early response protooncogenes c-jun, junB, fra-1, and fra-2 accompanied cell proliferation at low concentrations of PM whereas apoptotic concentrations of PM caused transient increases in expression of fos and jun family members and dose responsive increases in mRNA levels of receptor-interacting protein, Fas-associated death domain, and caspase-8. Significant increases in steady-state mRNA levels of protooncogenes and apoptosis-associated genes, TNFR-associated death domain, and Fas were also observed after exposure of epithelial cells to ufCB, but not fine carbon black or glass beads, respectively, suggesting that the ultrafine particulate component of PM is critical to its biological activity

Inhaled particulate matter causes expression of nuclear factor (NF)-kappa B-related genes and oxidant-dependent NF-kappa B 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 PM2.5 (particles of an aerodynamic diameter of < 2.5 microns) (300 μ g/m3 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)- κ B–associated and/ or –regulated genes, including tumor necrosis factor- α and - β , interleukin-6, interferon- γ , and transforming growth factor- β . Lung mRNA levels of lymphotoxin- β and macrophage migration inhibitory factor were unchanged. In murine C10 alveolar cells and an NF- κ B–luciferase reporter cell line, exposure to PM2.5 at noncytotoxic concentrations resulted in increases in transcriptional activation of NF- κ 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 ′ -7 ′ -dichlorofluoroscin diacetate, were observed in epithelial cells exposed to PM2.5 and ultrafine carbon black particles. Studies here are the first to show NF- κ B–related inflammatory and cytokine gene expression after inhalation of PM2.5 and oxidant-dependent induction of NF- κ B activity by PM2.5 in pulmonary epithelial cells