Rapid effects of diesel exhaust particulate extracts on intracellular signaling in human endothelial cells

Sumanasekera, Wasana; Ivanova, Margarita; Johnston, Benjamin J.; Dougherty, Susan; Суманасекера, Гамини; Myers, Steven R.; Ali, Yeakub; Kizu, Ryoichi; Klinge, Carolyn M.

doi:10.1016/j.toxlet.2007.08.014

Cited by 30 publications

(27 citation statements)

References 45 publications

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“…CSE and PM have been shown to impact the function of endothelium and cause altered gene expression in endothelial cells via their ability to generate ROS and nitrogen species (NOS) (Brunekreef, 2002; Donaldon et al, 2002; Hoshino et al, 2005; Mo et al, 2009; Orosz et al, 2007; Sumanasekera et al 2007). Several established risk factors for cardiovascular diseases have been linked to excessive ROS generation, known as a state of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Combination effects of cigarette smoke extract and ambient ultrafine particles on endothelial cells

Wan

Feng

et al. 2012

Toxicology in Vitro

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Previous studies have shown that ambient ultrafine particles with diameters less than 100 nm (UFPs) can pass from the lungs to the circulation because of their very small diameter, and induce lung oxidative stress with a resultant dysfunction of lung endothelial cells. However, no studies have addressed the potential combined effects of UFPs and cigarette smoke on vascular endothelial cells. We hypothesized that co-exposure to UFPs and cigarette smoke extract (CSE) may cause combined effects on activation of endothelial cells and dysfunction of endothelium by oxidative stress through activation of NADPH oxidase. We determined the effects of UFPs with or without CSE on mouse pulmonary microvascular endothelial cells (MPMVEC) obtained from C57BL/6J (wild-type) and gp91phox knock-out mice (gp91phox is one of the key components of NADPH oxidase, one of ROS generators). Our results showed that exposure of MPMVEC from wild-type mice to UFPs or CSE, at a non-toxic dose, induced reactive oxygen species (ROS) generation, increased phosphorylation of p38 and Erk1/2, and up-regulated early growth response -1 (Egr-1) and IL-6 genes. These effects were significantly enhanced when cells were co-exposed to both UFPs and CSE. However, exposure of MPMVEC from gp91phox knock-out mice did not induce the above effects. Furthermore, UFPs- and/or CSE-induced Egr-1 mRNA upregulation was attenuated significantly when cells were pre-treated with p38 specific inhibitor, SB 203580, or MEK1/2 inhibitor, PD98059, and Egr-1 siRNA treatment abolished UFPs- and/or CSE- induced overexpression of IL-6. Our results suggest that UFPs and/or CSE caused activation of NADPH oxidase, resulting in ROS generation that led to activation of MAPKs through induced phosphorylation of p38 and ERK1/2 MAPKs and upregulation of Egr-1. Those effects may further result in endothelial dysfunction through production of cytokines such as IL-6. Our results suggest that co-exposure to UFPs and CSE causes enhanced injury to endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Combination effects of cigarette smoke extract and ambient ultrafine particles on endothelial cells

Wan

Feng

et al. 2012

Toxicology in Vitro

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“…We previously characterized rapid non-genomic responses of primary bovine aortic endothelial cells (BAEC) and human umbilical vein endothelial cells (HUVECs) to estradiol (E 2 ), resveratrol, and organic diesel exhaust particulate extracts (DEPEs) collected from a diesel truck run at various speeds and engine loads (Klinge et al 2005; Klinge et al 2008; Sumanasekera et al 2007a; Sumanasekera et al 2007b). Our studies demonstrated that DEPEs from a truck run under increasing loads (L) stimulated phosphorylation of MAPK, AKT, and eNOS whereas DEPEs from the truck run at increasing speeds (S) did not affect MAPK alone, but inhibited E 2 -induced MAPK and endothelial nitric oxide synthase (eNOS) phosphorylation (Sumanasekera et al 2007a). Higher polyaromatic hydrocarbon (PAH) concentrations in the DEPE L compared to the DEPE S samples correlated with the differences in cellular activities.…”

Section: Introductionmentioning

confidence: 99%

Diesel exhaust particulate extracts inhibit transcription of nuclear respiratory factor-1 and cell viability in human umbilical vein endothelial cells

Mattingly

Klinge

2011

Arch Toxicol

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Endothelial dysfunction precedes cardiovascular disease and is accompanied by mitochondrial dysfunction. Here we tested the hypothesis that diesel exhaust particulate extracts (DEPEs), prepared from a truck run at different speeds and engine loads, would inhibit genomic estrogen receptor activation of nuclear respiratory factor-1 (NRF-1) transcription in human umbilical vein endothelial cells (HUVECs). Additionally, we examined how DEPEs affect NRF-1 regulated TFAM expression and, in turn, Tfam-regulated mtDNA-encoded cytochrome c oxidase subunit I (COI, MTCO1) and NADH dehydrogenase subunit I (NDI) expression as well as cell proliferation and viability. We report that 17β-estradiol (E2), 4-hydroxytamoxifen (4-OHT), and raloxifene increased NRF-1 transcription in HUVECs in an ER-dependent manner. DEPEs inhibited NRF-1 transcription and this suppression was not ablated by concomitant treatment with E2, 4-OHT, or raloxifene, indicating that the effect was not due to inhibition of ER activity. While E2 increased HUVEC proliferation and viability, DEPEs inhibited viability but not proliferation. Resveratrol increased NRF-1 transcription in an ER-dependent manner in HUVECs, and ablated DEPE inhibition of basal NRF-1 expression. Given that NRF-1 is a key nuclear transcription factor regulating genes involved in mitochondrial activity and biogenesis, these data suggest that DEPEs may adversely affect mitochondrial function leading to endothelial dysfunction and resveratrol may block these effects.

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“…These pro-oxidative effects are strongly linked to the induction of pro-infl ammatory responses in the same cell types as previously reviewed by Araujo ( 2011 ). These include the activation of the NF-kB Montiel-Davalos et al 2010 ), p38 MAPK (Mo et al 2009 ;Sumanasekera et al 2007 ) and ERK1/2 pathways (Mo et al 2009 ) with subsequent upregulation of pro-infl ammatory factors such as TNF-α, IL-8, and monocyte chemotactic protein-1 (MCP-1), Montiel-Davalos et al 2010 ), and adhesion molecules such as VCAM ), E-selectin, P-selectin (MontielDavalos et al 2007 ) in endothelial cells. There is also an air pollution induced increase in production of TNF-α, IL-6 (Alfaro- Moreno et al 2002 ;Fujii et al 2002 ;Osornio-Vargas et al 2003 ;Pozzi et al 2003 ;Becker et al 2005a ;Amakawa et al 2003 ), IL-8 (Becker et al 2005b ;Monn and Becker 1999 ), IL1-α (Brown et al 2004 ), IL1-β (Jimenez et al 2002 ), granulocyte macrophage colony-stimulating factor (GM-CSF) (Fujii et al 2002 ;Ishii et al 2005 ) and macrophage-infl ammatory protein-2 (MIP-2) (Imrich et al 2007 ) in macrophages.…”

Section: Role Of Ros and Infl Ammationmentioning

confidence: 80%

Air Pollution, Lipids and Atherosclerosis

Araujo

Rosenfeld

2015

Molecular and Integrative Toxicology

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Rapid effects of diesel exhaust particulate extracts on intracellular signaling in human endothelial cells

Cited by 30 publications

References 45 publications

Combination effects of cigarette smoke extract and ambient ultrafine particles on endothelial cells

Combination effects of cigarette smoke extract and ambient ultrafine particles on endothelial cells

Diesel exhaust particulate extracts inhibit transcription of nuclear respiratory factor-1 and cell viability in human umbilical vein endothelial cells

Air Pollution, Lipids and Atherosclerosis

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