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Toxicol Appl Pharmacol. 2015 May 1;284(3):281-291. doi: 10.1016/j.taap.2015.01.010. Epub 2015 Jan 22.

Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals.

Author information

1
Division of Cardiology, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095.
#
Contributed equally

Abstract

Diesel exhaust particles (DEPs) are a major component of diesel emissions, responsible for a large portion of their toxicity. In this study, we examined the toxic effects of DEPs on endothelial cells and the role of DEP-induced heme oxygenase-1 (HO-1) expression. Human microvascular endothelial cells (HMECs) were treated with an organic extract of DEPs from an automobile engine (A-DEP) or a forklift engine (F-DEP) for 1 and 4h. ROS generation, cell viability, lactate dehydrogenase leakage, expression of HO-1, inflammatory genes, cell adhesion molecules and unfolded protein respone (UPR) gene were assessed. HO-1 expression and/or activity were inhibited by siRNA or tin protoporphyrin (Sn PPIX) and enhanced by an expression plasmid or cobalt protoporphyrin (CoPPIX). Exposure to 25μg/ml of A-DEP and F-DEP significantly induced ROS production, cellular toxicity and greater levels of inflammatory and cellular adhesion molecules but to a different degree. Inhibition of HO-1 enzymatic activity with SnPPIX and silencing of the HO-1 gene by siRNA enhanced DEP-induced ROS production, further decreased cell viability and increased expression of inflammatory and cell adhesion molecules. On the other hand, overexpression of the HO-1 gene by a pcDNA 3.1D/V5-HO-1 plasmid significantly mitigated ROS production, increased cell survival and decreased the expression of inflammatory genes. HO-1 expression protected HMECs from DEP-induced prooxidative and proinflammatory effects. Modulation of HO-1 expression could potentially serve as a therapeutic target in an attempt to inhibit the cardiovascular effects of ambient PM.

KEYWORDS:

Air pollution; Diesel exhaust particles; Endothelial cells; Heme oxygenase-1; Inflammation; Reactive oxygen species

PMID:
25620054
PMCID:
PMC4743257
DOI:
10.1016/j.taap.2015.01.010
[Indexed for MEDLINE]
Free PMC Article

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