Diesel exhaust particles are taken up by human airway epithelial cells in vitro and alter cytokine production.
(1/958)
The involvement of diesel exhaust particles (DEPs) in respiratory diseases was evaluated by studying their effects on two in vitro models of human airway epithelial cells. The cytotoxicity of DEPs, their phagocytosis, and the resulting immune response were investigated in a human bronchial epithelial cell line (16HBE14o-) as well as in human nasal epithelial cells in primary culture. DEP exposure induced a time- and dose-dependent membrane damage. Transmission electron microscopy showed that DEPs underwent endocytosis by epithelial cells and translocated through the epithelial cell sheet. Flow cytometric measurements allowed establishment of the time and dose dependency of this phagocytosis and its nonspecificity with different particles (DEPs, carbon black, and latex particles). DEPs also induced a time-dependent increase in interleukin-8, granulocyte-macrophage colony-stimulating factor, and interleukin-1beta release. This inflammatory response occurred later than phagocytosis, and its extent seems to depend on the content of adsorbed organic compounds because carbon black had no effect on cytokine release. Furthermore, exhaust gas posttreatments, which diminished the adsorbed organic compounds, reduced the DEP-induced increase in granulocyte-macrophage colony-stimulating factor release. These results suggest that DEPs could 1) be phagocytosed by airway epithelial cells and 2) induce a specific inflammatory response. (+info)
Diesel exhaust particles induce NF-kappa B activation in human bronchial epithelial cells in vitro: importance in cytokine transcription.
(2/958)
Fine particles derived from diesel engines (diesel exhaust particles, DEP) have attracted attention, since their density in industrial countries seems related to the increased prevalence of pulmonary diseases. Previous studies have suggested that DEP have a potential to directly activate airway epithelial cells to produce and release inflammatory cytokines and mediators, and thus facilitate inflammatory responses in the lung. To elucidate the molecular mechanisms of their action, we studied here IL-8 gene expression, one of the important cytokines in inflammatory responses, by Northern blot analysis and run-on transcription assay. Suspended DEP (1-50 microgram/ml) increased the steady state levels of IL-8 mRNA, which was suggested to be largely due to increased transcriptional rates. Electrophoretic mobility shift assay demonstrated that DEP induced increased binding to the specific motif of NF-kappa B, but not of transcription factor AP-1. The luciferase reporter gene assay using wild-type and mutated NF-kappa B-binding sequences showed that DEP-induced NF-kappa B activation was involved in IL-8 transcription. Finally, both N-acetylcysteine and pyrrolidine dithiocarbamate attenuated the action of DEP on IL-8 mRNA expression, suggesting that oxidant-mediated pathway might be involved in its processes. These results suggested that DEP activate NF-kappa B, which might be an important mechanism of its potential to increase the expression of inflammatory cytokines in vitro. (+info)
Inhalation of diesel engine exhaust affects spermatogenesis in growing male rats.
(3/958)
We conducted experiments to determine whether diesel engine exhaust affects reproductive endocrine function in growing rats. The rats were assigned to three groups: a group exposed to total diesel engine exhaust containing 5.63 mg/m3 particulate matter, 4.10 ppm nitrogen dioxide, and 8.10 ppm nitrogen oxide; a group exposed to filtered exhaust without particulate matter; and a group exposed to clean air. Dosing experiments were performed for 3 months beginning at birth (6 hr/day for 5 days/week). Serum levels of testosterone and estradiol were significantly higher in animals exposed to total diesel exhaust and filtered exhaust (p < 0.05 for each group) as compared to the controls. Follicle-stimulating hormone was significantly decreased in the two groups exposed to diesel exhaust as compared to the control group (p < 0.05). Luteinizing hormone was significantly decreased in the total exhaust-exposed group as compared to the control and filtered groups (p < 0.05). Although testis weight did not show any significant difference among the groups, sperm production and activity of testicular hyaluronidase were significantly reduced in both exhaust-exposed groups as compared to the control group. Histological examination showed decreased numbers of step 18 and 19 spermatids in stage VI, VII, and VIII tubules in the testes of both diesel exhaust-exposed groups. This study suggests that diesel exhaust stimulates hormonal secretion of the adrenal cortex, depresses gonadotropin-releasing-hormone, and inhibits spermatogenesis in rats. Because these effects were not inhibited by filtration, the gaseous phase of the exhaust appears to be more responsible than particulate matter for disrupting the endocrine system. (+info)
Diesel exhaust exposure among adolescents in Harlem: a community-driven study.
(4/958)
OBJECTIVES: This study sought individual-level data on diesel exhaust exposure and lung function among adolescents in Harlem as part of a community-driven research agenda. METHODS: High school students administered in-person surveys to seventh grade students to ascertain information on demographics, asthma history, and self-reported and maternal smoking. Urine samples were assayed for 1-hydroxypyrene (1-HP), a marker of diesel exhaust exposure, and cotinine, a marker of tobacco smoke exposure. Computer-assisted spirometry was used to measure lung function. RESULTS: Three quarters (76%) of the participating students had detectable levels of 1-HP. Three students (13%) had an FEF25-75 of less than or equal to 80% of their predicted measurements, and 4 students (17%) had results between 80% and 90% of the predicted value, all of which are suggestive of possible lung impairment. CONCLUSIONS: These data suggest that most adolescents in Harlem are exposed to detectable levels of diesel exhaust, a known exacerbator and possible cause of chronic lung disorders such as asthma. Community-driven research initiatives are important for empowering communities to make needed changes to improve their environments and health. (+info)
Occupational exposure to diesel exhaust and lung cancer: a meta-analysis.
(5/958)
OBJECTIVES: We undertook a meta-analysis of epidemiological studies investigating the relationship between occupational diesel exhaust exposure and lung cancer. METHODS: Thirty of 47 studies initially identified as potentially relevant met specified inclusion criteria. We extracted or calculated 39 independent estimates of relative risk and derived pooled estimates of risk for all studies and for numerous study subsets by using a random-effects model. We also examined interstudy heterogeneity by using linear metaregressions. RESULTS: There was substantial heterogeneity in the pooled risk estimates for all studies combined and for most subsets. Several factors consistent with higher study quality, however, contributed to increased pooled estimates of risk and lower heterogeneity, including (1) adjustment for confounding by cigarette smoking and other covariates, (2) having a lower likelihood of selection bias, and (3) having increased study power. CONCLUSION: This analysis provides quantitative support for prior qualitative reviews that have ascribed an etiologic role to occupational diesel exhaust exposure in lung cancer induction. Among study populations most likely to have had substantial exposure to diesel exhaust, the pooled smoking-adjusted relative risk was 1.47 (95% confidence interval = 1.29, 1.67). (+info)
Enhancement of collagen-induced arthritis in mice by diesel exhaust particles.
(6/958)
The present study was undertaken to investigate the effect of diesel exhaust particles (DEP) on collagen-induced arthritis (CIA), which is an experimental model of autoimmune disease, in mice. CIA was induced by s.c. injection of type II collagen (CII) emulsified with complete Freund's adjuvant into the base of the tail (day 0) followed by a booster injection on day 21. Varying doses of DEP were intranasally administered every 2 days from days 0 to 20. The results showed that administration of DEP enhanced both the incidence and the severity of CIA. The enhancement of the disease was associated with pronounced production of anti-CII IgG and IgG2a antibodies. Treatment with DEP also augmented proliferative responses of spleen cells to CII. There was marked secretion of interferon-gamma, interleukin (IL)-2, and IL-4 from the lymphoid cells in DEP-treated mice. Administration of DEP after onset of CIA was also effective in enhancing the severity of the disease as well as production of anti-CII IgG and IgG2a antibodies and secretion of interferon-gamma, IL-2, and IL-4. These results suggest that exposure to DEP may influence autoimmune disease. (+info)
Changes in levels of 8-hydroxyguanine in DNA, its repair and OGG1 mRNA in rat lungs after intratracheal administration of diesel exhaust particles.
(7/958)
Diesel exhaust particles (DEP), an environmental pollutant, are known to induce lung cancer in experimental animals. To clarify whether reactive oxygen species (ROS) are involved in its carcinogenic mechanism, we examined the levels of 8-hydroxyguanine (8-OH-Gua), its total repair and the repair enzyme OGG1 mRNA in female Fischer 344 rat lungs, as markers of the response to ROS, after DEP was intratracheally instilled. The 8-OH-Gua levels in both DEP-treated groups (2 and 4 mg) were increased during the 2-8 h following exposure to DEP. The 8-OH-Gua repair activities in the DEP-treated groups decreased during the period from 2 h to 2 days following DEP exposure and then recovered to the level of the control group at 5 days after exposure. OGG1 mRNA was induced in rats treated with 4 mg DEP for 5-7 days after administration. In conclusion, the 8-OH-Gua level in rat lung DNA increases markedly at an early phase after DEP exposure, by the generation of ROS and the inhibition of 8-OH-Gua repair activity, and induction of OGG1 mRNA is also a good marker of cellular oxidative stress during carcinogenesis. (+info)
Generation of reactive oxygen species and 8-hydroxy-2'-deoxyguanosine formation from diesel exhaust particle components in L1210 cells.
(8/958)
The generation of the reactive oxygen species during the interaction of diesel exhaust particles (DEP) with NADPH-cytochrome P450 reductase (P450 reductase) was investigated by electron spin resonance using the spin-trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO). Addition of DEP extract to an incubation mixture of mouse lung microsomes in the presence of NADPH resulted in a time-dependent NADPH oxidation and acetylated-cytochrome c reduction. Using purified P450 reductase as the enzyme source, superoxide radicals which were detected as the spin adduct (DMPO-OOH) while metabolized by P450 reductase were dependent upon both DEP and enzyme concentrations. The ELISA method using a specific monoclonal antibody revealed that DEP produced 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is formed from deoxyguanosine in DNA by hydroxyl radicals, in the culture medium of L1210 cells. Active oxygen scavengers such as superoxide dismutase and catalase effectively blocked the formation of 8-OHdG in culture medium, and deferoxamine, which inhibits hydroxyl radicals production by chelating iron, was also effective in inhibiting the DEP-produced 8-OHdG formation. These results indicate that DEP components produce 8-OHdG through the hydroxyl radical formation via superoxide by redox cycling of P450 reductase. (+info)