Exposure to metal-rich particulate matter modifies the expression of candidate microRNAs in peripheral blood leukocytes

Background: Altered 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.Objectives: We 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.Methods: We 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 microm in aerodynamic diameter), PM10 (< 10 microm in aerodynamic diameter), coarse PM (PM10 minus PM1), and PM metal components (chromium, lead, cadmium, arsenic, nickel, manganese) between the baseline and postexposure measurements.Results: Expression of miR-222 and miR-21 (using the 2-DeltaDeltaCT 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 (beta = 0.41, p = 0.02), whereas miR-21 expression was associated with blood 8-hydroxyguanine (beta = 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 (beta = -0.51, p = 0.011) and cadmium (beta = -0.42, p = 0.04).Conclusions: Changes in miRNA expression may represent a novel mechanism mediating responses to PM and its metal components. Editor's SummaryExposure to ambient particulate matter (PM) has been associated with adverse health effects, including morbidity and mortality from cardiovascular and respiratory diseases. The literature suggests an association between exposure to PM and systemic activation of inflammatory pathways, production of reactive oxygen species, and enhanced coagulation, but the mechanism for such effects remains undetermined. Bollati et al. (p. 763) estimated associations between exposure to PM and PM metal components and the expression of microRNAs (miRNAs) relevant to oxidative stress and inflammatory processes in peripheral blood mononuclear cells collected from 63 workers at an electric-furnace steel plant. MiR-222 and miR-21 expression was significantly increased in postexposure samples, and miR-222 expression was positively associated with lead exposure. MiR-21 expression was also associated with the 8-hydroxyguanine content of mitochondrial DNA, but not with individual PM size fractions or metal components. Postexposure expression of miR-146a was not significantly different from baseline but was inversely associated with exposure to lead and cadmium. The authors conclude that changes in miRNA expression may represent a novel mechanism that mediates responses to PM and its metal components.