Cytokine responses induced by diesel exhaust particles are suppressed by PAR-2 silencing and antioxidant treatment, and driven by polar and non-polar soluble constituents.

Abstract

Adsorbed soluble organics seem to be the main drivers of inflammatory responses induced by diesel exhaust particles (DEP). The specific compounds contributing to this process and the cellular mechanisms behind DEP-induced inflammation are not well known. We have assessed pro-inflammatory effects of DEP and various soluble DEP fractions, in human bronchial epithelial cells (BEAS-2B). DEP increased the expression of interleukin (IL)-6 and CXCL8. Silencing of the aryl hydrocarbon receptor (AhR) by siRNA or pretreatment with AhR-antagonists did not attenuate DEP-induced IL-6 and CXCL8 responses. However, the halogenated aromatic hydrocarbon (HAH)-selective AhR antagonist CH223191 caused a considerable reduction in DEP-induced CYP1A1 expression indicating that this response may be due to dioxin or dioxin-like constituents in DEP. Knock-down of protease activated receptor (PAR)-2 attenuated IL-6 responses without affecting CXCL8. Antioxidants did not affect IL-6 expression after 4h DEP-exposure and only partly reduced CXCL8 expression. However, after 24h exposure antioxidant treatment partly suppressed IL-6 protein release and completely blocked CXCL8 release. Furthermore, a heptane-soluble (non-polar) extract of DEP induced both IL-6 and CXCL8 release, whereas a PBS-soluble (highly polar) extract induced only IL-6. Thus, pro-inflammatory responses in DEP-exposed epithelial cells appear to be the result of both reactive oxygen species and receptor signaling, mediated through combinatorial effects between both non-polar and polar constituents adhered to the particle surface.

• Authors: Nicolai Bach, Anette Kocbach Bølling, Bendik C Brinchmann, Annike I Totlandsdal, Tonje Skuland, Jørn A Holme, Marit Låg, Per E Schwarze, Johan Øvrevik
• Journal: Toxicology letters (Toxicol Lett) Vol. 238 Issue 2 Pg. 72-82 (Oct 14 2015) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 26160521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• AHR protein, human
• Antioxidants
• Basic Helix-Loop-Helix Transcription Factors
• CXCL8 protein, human
• Cytokines
• Heptanes
• IL6 protein, human
• Inflammation Mediators
• Interleukin-6
• Interleukin-8
• Particulate Matter
• Receptor, PAR-2
• Receptors, Aryl Hydrocarbon
• Solvents
• TLR3 protein, human
• Toll-Like Receptor 3
• Vehicle Emissions
• CYP1A1 protein, human
• Cytochrome P-450 CYP1A1
• Methanol

Topics

• Antioxidants (pharmacology)
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
• Cell Line
• Cytochrome P-450 CYP1A1 (metabolism)
• Cytokines (metabolism)
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects, immunology, metabolism)
• Heptanes (chemistry)
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-6 (metabolism)
• Interleukin-8 (metabolism)
• Lung (drug effects, immunology, metabolism)
• Methanol (chemistry)
• Oxidative Stress (drug effects)
• Particulate Matter (chemistry, toxicity)
• RNA Interference
• Receptor, PAR-2 (drug effects, genetics, metabolism)
• Receptors, Aryl Hydrocarbon (genetics, metabolism)
• Solubility
• Solvents (chemistry)
• Time Factors
• Toll-Like Receptor 3 (agonists, metabolism)
• Transfection
• Vehicle Emissions (toxicity)