Coarse particulate matter (PM2.5\u201310) in Los Angeles Basin air induces expression of inflammation and cancer biomarkers in rat brains

Julia Y Ljubimova,Michael T Kleinman,Rameshwar Patil,Oliver Braubach,Ekaterina S Shatalova,Anna Galstyan,Keith L Black,Eggehard Holler,Jie Tang,Antonella Chiechi

doi:10.1038/s41598-018-23885-3

Abstract

Air pollution is linked to brain inflammation, which accelerates tumorigenesis and neurodegeneration. The molecular mechanisms that connect air pollution with brain pathology are largely unknown but seem to depend on the chemical composition of airborne particulate matter (PM). We sourced ambient PM from Riverside, California, and selectively exposed rats to coarse (PM2.5–10: 2.5–10 µm), fine (PM<2.5: <2.5 µm), or ultrafine particles (UFPM: <0.15 µm). We characterized each PM type via atomic emission spectroscopy and detected nickel, cobalt and zinc within them. We then exposed rats separately to each PM type for short (2 weeks), intermediate (1–3 months) and long durations (1 year). All three metals accumulated in rat brains during intermediate-length PM exposures. Via RNAseq analysis we then determined that intermediate-length PM2.5–10 exposures triggered the expression of the early growth response gene 2 (EGR2), genes encoding inflammatory cytokine pathways (IL13-Rα1 and IL-16) and the oncogene RAC1. Gene upregulation occurred only in brains of rats exposed to PM2.5–10 and correlated with cerebral nickel accumulation. We hypothesize that the expression of inflammation and oncogenesis-related genes is triggered by the combinatorial exposure to certain metals and toxins in Los Angeles Basin PM2.5–10.

Highlights

Air pollution leads to well-documented cardiovascular and respiratory problems[1,2], brain cancer, and neurological disorders including strokes, Alzheimer’s, and Parkinson’s disease[3,4,5,6,7]
Upregulation of inflammation and tumorigenesis biomarkers was only observed following exposures to PM2.5–10, not ultrafine particulate matter (UFPM). We explain this finding by comparing the unique toxicological profiles of PM2.5–10 and UFPM; both contain metals, but only PM2.5–10 correlates with ambient endotoxin concentrations in Southern California[27,28]
Via inductively coupled plasma atomic emission spectroscopy (ICP-AES), we first analyzed the metal content of our particulate matter (PM) samples and asked if these metals accumulated in the brains of rats that were exposed to PM

Summary

Introduction

Air pollution leads to well-documented cardiovascular and respiratory problems[1,2], brain cancer, and neurological disorders including strokes, Alzheimer’s, and Parkinson’s disease[3,4,5,6,7]. To better understand the biological mechanisms that underlie pollution-associated brain disorders, we must identify disease causing components in air pollution mixtures; these include gases, particulate matter (PM), trace metals, and organic compounds. Upregulation of inflammation and tumorigenesis biomarkers was only observed following exposures to PM2.5–10, not UFPM We explain this finding by comparing the unique toxicological profiles of PM2.5–10 and UFPM; both contain metals, but only PM2.5–10 correlates with ambient endotoxin concentrations in Southern California[27,28]. This suggests that combinatorial exposures to multiple toxins are necessary to trigger certain molecular events that precede inflammation and tumorigenesis

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Conclusion