Real-world PM extracts differentially enhance Th17 differentiation and activate the aryl hydrocarbon receptor (AHR). (15th February 2019)

• Record Type: Journal Article
• Authors: O'Driscoll, Chelsea A.; Gallo, Madeline E.; Fechner, John H.; Schauer, James J.; Mezrich, Joshua D.
• Is Part Of: Toxicology. Volume 414(2019)
• Page Start: 14
• Page End: 26
• Publication Date: 2019-02-15
• Subjects: Atmospheric particulate matter -- Chemically-Extracted organic fraction -- Th17 differentiation -- Polycyclic aromatic hydrocarbons -- Aryl hydrocarbon receptor; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2019.01.002
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: Organic extracts of real-world samples differentially enhance Th17 differentiation. Organic extracts of real-world samples activate the AHR to varying degrees. Specific PAHs in PM, not sum concentration of PAHs, may control the immune response. Not all PM samples behave the same. PM samples with more PAHs do not necessarily have the strongest response. 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.