Ambient PM Toxicity Is Correlated with Expression Levels of Specific MicroRNAs

Uncertainties
regarding 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 tumor necrosis factor-α (TNF-α)
and monocyte chemoattractant protein-1 (MCP-1) levels were detected
following the second and third PM injections. Rats’ inflammatory
responses varied substantially with the injections of city-specific
PMs. Repeated PM extract exposure rendered the rats more vulnerable
to subsequent challenges, and downregulation of certain microRNAs
was 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 a 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 that certain microRNAs, e.g., miR-125b and miR-21, may
be externally mediated to neutralize PM-related health damages.