Ambient PM Toxicity Is Correlated with Expression Levels of Specific MicroRNAs

Abstract

Uncertainties for optimized air pollution control remain as the underlying mechanisms of city-specific ambient particulate matter (PM)-induced health effects are unknown. Here, water-soluble extracts of PMs collected from four global cities via automobile air conditioning filters were consecutively injected three times by an amount of 1, 2 and 2 mg into the blood circulation of Wistar rats after filtration by a 0.45 µm pore size membrane. Acute health effects such as immune and inflammatory responses and hemorrhage in alveoli were observed right after the PM extraction injection. Significant differences between cities in biomarker TNF-α and MCP-1 levels were detected following the second and third PM injections. Rats’ inflammation responses varied substantially with the injections of city-specific PMs. Repeated PM extract exposure rendered the rats more vulnerable to subsequent challenges; and down-regulations of certain microRNAs were observed in rats. Among the studied miRNAs, miR-125b and miR-21 were most sensitive to the PM exposure, exhibiting a negative dose-response type relationship with source-specific PM (oxidative potential) toxicity (r2=0.63 and 0.57; p-values<0.05). The results indicated that city-specific PMs could induce different health effects by selectively regulating different miRNAs; and certain microRNAs, e.g., miR-125b and miR-21, may be externally mediated to neutralize PM-related health damages.