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Real-world PM extracts differentially enhance Th17 differentiation and activate the aryl hydrocarbon receptor (AHR)
- Publication Year :
- 2019
-
Abstract
- Atmospheric particulate matter (PM) is a complex component of air pollution and the leading environmental risk factor for death worldwide. PM is formed from a combination of primary sources that emit PM directly into the atmosphere and secondary sources that emit gaseous precursors which oxidize in the atmosphere to form PM and composed of both inorganic and organic components. Currently, all PM is regulated by total mass. This regulatory strategy does not consider individual chemical constituents and assumes all PM is equally toxic. The chemically-extracted organic fraction (OF) of PM retains most organic constituents such as polycyclic aromatic hydrocarbons (PAHs) and excludes inorganics. PAHs are ubiquitous environmental toxicants and known aryl hydrocarbon receptor (AHR) ligands. This study addressed the role of individual components, specifically PAHs, of PM and how differences in chemical composition of real-world samples drive differential responses. This study tested the hypothesis that real-world extracts containing different combinations and concentrations of PAHs activate the AHR and enhance T helper (Th)17 differentiation to different degrees based on specific PAHs present in each sample, and not simply the mass of PM. The ability of the real-world OF, with different PAH compositions, to enhance Th17 differentiation and activate the AHR was tested in vitro. Cumulatively, the results identified PAHs as possible candidate components of PM contributing to increased inflammation and demonstrated that the sum concentration of PAHs does not determine the extent to which each PM activates the AHR and enhances Th17 differentiation suggesting individual components of each PM, and interactions of those components with others in the mixture, contribute to the inflammatory response. This demonstrates that not all PM are the same and suggests that when regulating PM based on its ability to cause human pathology, a strategy based on PM mass may not reduce pathologic potential of exposures.
- Subjects :
- 0301 basic medicine
Male
Inflammatory response
Toxicology
Risk Assessment
Article
03 medical and health sciences
0302 clinical medicine
Basic Helix-Loop-Helix Transcription Factors
Cytochrome P-450 CYP1A1
Th17 differentiation
Animals
Polycyclic Aromatic Hydrocarbons
Cells, Cultured
Air Pollutants
biology
Dose-Response Relationship, Drug
Chemistry
Cell Differentiation
Particulates
Th1 Cells
Aryl hydrocarbon receptor
Organic fraction
Mice, Inbred C57BL
030104 developmental biology
Receptors, Aryl Hydrocarbon
Environmental chemistry
Chemical constituents
Enzyme Induction
biology.protein
Female
Particulate Matter
Organic component
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....8e22e9b445fcff027020dbf6451cc0d1