Induction of Inflammatory Responses in Human Bronchial Epithelial Cells by Pb²⁺-Containing Model PM_2.5 Particles via...

Airborne particular matter (PM_2.5) contains complex mixtures of pollutants, and their compositions also vary with time and location. Inhalation of PM_2.5 may cause a number of diseases, such as bronchial and lung inflammation and lung cancer. So far, how different components of PM_2.5 contribute to inflammation and toxicity is still not known. To identify key PM_2.5 components that are responsible for inflammation, here we took a reductionism approach and synthesized a model PM_2.5 library containing 20 carbon nanoparticle based members with loadings of As(III), Pb²⁺, Cr(VI), and BaP individually or in combination at environment relevant concentrations. We discovered that only carbon nanoparticle-Pb²⁺ adducts, not other pollutants or adducts, induced inflammation in human bronchial cells by suppressing the expression of a novel long noncoding RNA lnc-PCK1-2:1, while lnc-PCK1-2:1 routinely plays a regulatory role in inhibiting inflammation. This finding was further substantiated by varying Pb²⁺ loadings on carbon nanoparticles and overexpressing lnc-PCK1-2:1. The success of this approach opens an avenue for further elucidation of molecular mechanisms of PM_2.5-induced inflammation and toxicity.