Organic chemicals from diesel exhaust particles affects intracellular calcium, inflammation and β-adrenoceptors in endothelial cells. (1st March 2019)

• Record Type: Journal Article
• Authors: Brinchmann, Bendik C.; Le Ferrec, Eric; Podechard, Normand; Lagadic-Gossmann, Dominique; Holme, Jørn A.; Øvrevik, Johan
• Is Part Of: Toxicology letters. Volume 302(2019)
• Page Start: 18
• Page End: 27
• Publication Date: 2019-03-01
• Subjects: AhR aryl hydrocarbon receptor -- βAR β-adrenoceptors -- B[a]P benzo[a]pyrene -- Ca2+ calcium -- CVD cardiovascular disease -- n-Hex-EOM DEP extracted by: n-hexane -- DCM-EOM dichloromethane -- Methanol-EOM methanol -- Water-EOM water at 25 °C -- DEP diesel exhaust particles -- eNOS endothelial nitric oxide synthase -- DEP-EOM extractable organic material of DEP -- HMEC-1 human microvascular endothelial cell-line -- HEK293 human embryonic kidney cells -- WT wild type -- [Ca2+]i intracellular calcium concentrations -- IP3 inositol trisphosphate -- GPCR G-protein coupled receptors -- PM particulate matter -- PAR-2 protease-activated receptor-2 -- PAHs polycyclic aromatic hydrocarbons -- NF-κB nuclear factor-κB -- 1-NP 1-nitro-pyrene -- DMSO dimethyl sulfoxide -- COX-2 cyclooxygenase 2 -- CXCL8 interleukin 8 -- MMP-1 matrix metalloproteinase 1; Diesel exhaust particles -- Extractable organic material -- Endothelial dysfunction -- Calcium signaling -- Beta adrenoceptors -- Protease activated receptor; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2018.11.009
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Organic chemicals from DEP enhanced [Ca2+]i and inflammation-associated genes in HMEC-1 endothelial cells. Organic chemicals extracted from DEP by dichloromethane enhanced [Ca2+]i via β-adrenoceptors and protease activated receptor 2. Effects of organic chemicals extracted from DEP by dichloromethane on COX-2 expression depended partly on enhanced [Ca2+]i and β-adrenoceptors. Abstract: Exposure to diesel exhaust particles (DEP) may contribute to endothelial dysfunction and cardiovascular disease. DEP, extractable organic material from DEP (DEP-EOM) and certain PAHs seem to trigger [Ca 2+ ] i increase as well as inflammation via GPCRs like βARs and PAR-2. In the present study we explored the involvement of βARs and PAR-2 in effects of DEP-EOM on [Ca 2+ ] i and expression of inflammation-associated genes in the endothelial cell-line HMEC-1. We exposed the human microvascular endothelial cell line HMEC-1 to DEP-EOM fractionated by sequential extraction with solvents of increasing polarity: n -hexane ( n -Hex-EOM), dichloromethane (DCM-EOM), methanol (Methanol-EOM) and water (Water-EOM). While Methanol-EOM and Water-EOM had no marked effects, n -Hex-EOM and DCM-EOM enhanced [Ca 2+ ] i (2–3 times baseline) and expression of inflammation-associated genes (IL-1α, IL-1β, COX-2 and CXCL8; 2–15 times baseline) in HMEC-1. The expression of βARs (60–80% of baseline) and βAR-inhibitor carazolol suppressed the increase in [Ca 2+ ] i induced by both n -Hex- and DCM-EOM. Carazolol as well as the Ca 2+ -channel inhibitor SKF-96365 reduced the DCM-EOM-induced pro-inflammatory gene-expression. Overexpression of βARs increased DCM-EOM-induced [Ca 2+ ] i responses in HEK293 cells, while βAR-overexpression suppressed [Ca 2+ ] i responses from n -Hex-EOM. Furthermore, the PAR-2-inhibitor ENMD-1068 attenuated [Ca 2+ ] i responses to DCM-EOM, but not n -Hex-EOM in HMEC-1. The results suggest that βAR and PAR-2 are partially involved in effects of complex mixtures of chemicals extracted from DEP on calcium signalling and inflammation-associated genes in the HMEC-1 endothelial cell-line.