Exposure to Metal-Rich Particulate Matter Modifies the Expression of Candidate MicroRNAs in Peripheral Blood Leukocytes

Abstract

BackgroundAltered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs that regulate the expression of broad gene networks at the posttranscriptional level.ObjectivesWe evaluated the effects of exposure to PM and PM metal components on candidate miRNAs (miR-222, miR-21, and miR-146a) related with oxidative stress and inflammatory processes in 63 workers at an electric-furnace steel plant.MethodsWe measured miR-222, miR-21, and miR-146a expression in blood leukocyte RNA on the first day of a workweek (baseline) and after 3 days of work (postexposure). Relative expression of miRNAs was measured by real-time polymerase chain reaction. We measured blood oxidative stress (8-hydroxyguanine) and estimated individual exposures to PM1 (< 1 μm in aerodynamic diameter), PM10 (< 10 μm in aerodynamic diameter), coarse PM (PM10 minus PM1), and PM metal components (chromium, lead, cadmium, arsenic, nickel, manganese) between the baseline and postexposure measurements.ResultsExpression of miR-222 and miR-21 (using the 2−ΔΔCT method) was significantly increased in postexposure samples (miR-222: baseline = 0.68 ± 3.41, postexposure = 2.16 ± 2.25, p = 0.002; miR-21: baseline = 4.10 ± 3.04, postexposure = 4.66 ± 2.63, p = 0.05). In postexposure samples, miR-222 expression was positively correlated with lead exposure (β = 0.41, p = 0.02), whereas miR-21 expression was associated with blood 8-hydroxyguanine (β = 0.11, p = 0.03) but not with individual PM size fractions or metal components. Postexposure expression of miR-146a was not significantly different from baseline (baseline = 0.61 ± 2.42, postexposure = 1.90 ± 3.94, p = 0.19) but was negatively correlated with exposure to lead (β = −0.51, p = 0.011) and cadmium (β = −0.42, p = 0.04).ConclusionsChanges in miRNA expression may represent a novel mechanism mediating responses to PM and its metal components.

Analysis of plasma microRNA expression profiles in a Chinese population occupationally exposed to benzene and in a population with chronic benzene poisoning

“…Actually, previous studies demonstrated that miRNAs may exhibit different functions and expression changes to adapt environmental stress or maintain the state of malignancy (23,35). These results again indicated that miRNA profile implies the distinct mechanisms of chemical which induced biological or pathological consequences (11,36).…”

“…miRNAs play crucial roles in a broad range of physiological and pathological processes, including the processes of normal hematopoiesis and hematopoietic malignancies progression (7)(8)(9). Simultaneously, growing evidences have indicated that exposure to hazardous environmental factors may significantly disrupt miRNA expression patterns (10)(11)(12). Previous studies also revealed that dysregulated miRNAs are involved in responses to polycyclic aromatic hydrocarbons (PAHs) (13).…”

Ambient Particulate Air Pollution, Environmental Tobacco Smoking, and Childhood Asthma: Interactions and Biological Mechanisms

“…Alveolar epithelial and pulmonary endothelial cells (9) and fibroblasts (10) from the lungs of patients with emphysema exhibit shorter telomeres, compared with those from subjects without emphysema. Recent data also indicate that telomeres in circulating leukocytes from patients with COPD are shorter, compared with control subjects in any age range (11,12).…”

Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

“…The epigenetic effects of cadmium in humans are supported by increased expression of miRNA-146a detected in peripheral white blood cells from workers who were exposed to cadmium by inhalation (Bollati et al 2010). The increased expression of miRNA-146a by cadmium may represent inflammatory response because miRNA-146 expression is known to be regulated by the NF-κB transcription factor, involved in inflammation and innate immunity (Williams et al 2008;Curtale et al 2010).…”