Induction of Inflammatory Responses in Human Bronchial Epithelial Cells by Pb²⁺-Containing Model PM_2.5 Particles via Downregulation of a Novel Long Noncoding RNA lnc-PCK1-2:1

Abstract

Airborne particular matter (PM2.5) contains complex mixtures of pollutants, and their compositions also vary with time and location. Inhalation of PM2.5 may cause a number of diseases, such as bronchial and lung inflammation and lung cancer. So far, how different components of PM2.5 contribute to inflammation and toxicity is still not known. To identify key PM2.5 components that are responsible for inflammation, here we took a reductionism approach and synthesized a model PM2.5 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 PM2.5-induced inflammation and toxicity.

Interactions of particulate matter and pulmonary surfactant: Implications for human health

“…Pan et al . [ 227 ] also proved recently that pure carbon black did not induce inflammation to human bronchial cells. Nevertheless, when carbon nanoparticles formed adducts with Pb 2+ and incubated with human lung cells, the expression of the long novel noncoding RNA which is responsible for the regulation of inflammation was depressed.…”

Antagonistic role of Al3+ against PM2.5-induced neurotoxicity via suppression of NADPH oxidase-triggered oxidative stress

“…Model PM 2.5 was synthesized with the published method by our group. 33 CNPs were chosen as supportive materials and five key pollutants Al 3+ , Pb 2+ , As( iii ), Cr( vi ) and BaP were selected for surface adsorption. Various concentrations of pollutants were mixed with CNPs.…”

“…Herein, model PM 2.5 particles were fabricated based on carbon nanoparticles (CNPs) according to our previous report. 33 Five key pollutants, including Al 3+ , Pb 2+ , As( iii ), Cr( vi ) and benzo[ a ]pyrene (BaP), were chosen and loaded onto our model PM 2.5 particles. Among them, Pb 2+ and BaP are well-known neurotoxicants.…”

Deciphering the Code between Air Pollution and Disease: The Effect of Particulate Matter on Cancer Hallmarks

“…Transition metals contained in PM 10 and PM 2.5 are partially responsible for TNF-α and IL6 release in macrophages [65]. However, other components of PM are responsible for inflammatory responses, including PAHs [26], activation of AHR [46], upregulation of CYP1A1 and CYP1B1 genes [66], hypomethylation in genes linked to cytokine and immune responses [45], upregulation of miR-146a [67], and suppression of a long non-coding RNA (lnc-PCK1-2:1) [68]. The inflammatory response induced by PM or by some PM components has been well demonstrated in several cell linages including blood mononuclear cells [69], natural killer cells [70], T cells [71], human pulmonary fibroblasts [72], but also in lung tissue of rats exposed to PM 10 [73] and circulating monocytes and T lymphocytes from humans environmentally exposed [74], as well as in BALB/c mice [75].…”