DEP induction of ROS in capillary-like endothelial tubes leads to VEGF-A expression

Abstract

Inhalation of diesel exhaust particles (DEPs) is associated with pulmonary and cardiovascular disease. One contributor to pathogenesis is inhaled particles reaching and injuring the lung capillary endothelial cells, and possibly gaining access to the blood stream. Using in vitro capillary tubes as a simplified vascular model system for this process, it was previously shown that DEPs induce the redistribution of vascular endothelial cell-cadherin (VE-Cad) away from the plasma membrane to intracellular locations. This allowed DEPs into the cell cytoplasm and tube lumen, suggesting the tubes may have become permeable (Chao et al., 2011). Here some of the mechanisms responsible for endothelial tube changes after DEP exposure were examined. The results demonstrate that endothelial tube cells mounted an oxidative stress response to DEP exposure. Hydrogen peroxide and oxidized proteins were detected after 24 hr of exposure to DEPs. Particles induced relocalization of Nrf2 from the cytoplasm to the nucleus, upregulating the expression of the enzyme heme oxygenase-1 (HO-1). Surprisingly, vascular endothelial cell growth factor-A (VEGF-A), initially termed “vascular permeability factor” (VPF), was found to be up-regulated in response to the HO-1 expression induced by DEPs. Similar to DEPs, applied VEGF-A induced relocalization of VE-Cadherin from the cell membrane surface to an intracellular location, and relocalization of VE-cadherin was associated with permeability. These data suggest that the DEPs may induce or contribute to the permeability of capillary-like endothelial tube cells via induction of HO-1 and VEGF-A.

Exposure to Diesel Exhaust Particle Extracts (DEPe) Impairs Some Polarization Markers and Functions of Human Macrophages through Activation of AhR and Nrf2

“…Signalling pathways putatively involved in DEPe-altered secretion capacity of polarizing MΦ were then analyzed. For this purpose, we studied the putative contribution of AhR and Nrf2 pathways because (i) DEP contain some aryl hydrocarbons well known as AhR ligands, (ii) AhR can interfere with the LPS-TLR4 signalling pathway [ 37 ], (iii) DEP leads to nuclear Nrf2 translocation [ 38 ] and (iv) exposure to particulate matter results in production of more pro-inflammatory cytokines [ 21 ] and CCL17 chemokine [ 20 ] in Nrf2-deficient mice than in the wild-type mice. As shown in Fig.…”

Exposure to PM2.5 causes genetic changes in fetal rat cerebral cortex and hippocampus

“…Inflammatory responses caused by oxidative stress affect neurological functions (Pope et al, ) and cause loss of blood vessel function (Ikeda et al, ). Our previous research systematically showed that PM 2.5 increased the release of intracellular free radicals, increased antioxidative protein HO‐1, increased expression levels of TNF‐α and IL‐6 cytokines, released vascular permeability factor VEGF‐A, and changed the distribution of endothelial cadherin protein before finally entering the blood circulation (Chao et al, ).…”

In vitroeffect of 4-pentylphenol and 3-methyl-4-nitrophenol on murine splenic lymphocyte populations and cytokine/granzyme production

“…Recent studies have shown that DEP exposure may help to generate reactive oxygen species (ROS) (Chao et al 2012;Vattanasit et al 2014) and decrease specific activities of superoxide dismutase (SOD), glutathione peroxidase (GSHPX) and glutathione reductase (GSHRX) in cells. DEP is also known to cause increases in lipid peroxidation, oxidative stress and DNA damage in human A549 lung epithelial cells and murine RAW 264.7 macrophages (Durga et al 2014).…”