Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/- mice and cultured endothelial cells.

Accumulating evidences indicate that pulmonary exposure to carbon nanotubes (CNTs) is associated with increased risk of lung diseases, whereas the effect on the vascular system is less studied. We investigated vascular effects of 2 types of multiwalled CNTs (MWCNTs) in apolipoprotein E(-/-) mice, wild-type mice, and cultured cells. The ApoE(-/-) mice had accelerated plaque progression in aorta after 5 intracheal instillations of MWCNT (25.6 µg/mouse weekly for 5 weeks). The exposure was associated with pulmonary inflammation, lipid peroxidation, and increased expression of inflammatory, oxidative stress, DNA repair, and vascular activation response genes. The level of oxidatively damaged DNA in lung tissue was unaltered, probably due to increased DNA repair capacities. Despite upregulation of inflammatory genes in the liver, effects on systemic cytokines and lipid peroxidation were minimal. The exposure to MWCNTs in cultured human endothelial cells increased the expression of cell adhesion molecules (ICAM1 and VCAM1). In cocultures, there was increased adhesion of monocytes to endothelial cells after exposure to MWCNT. The exposure to both types of MWCNT was also associated with increased lipid accumulation in monocytic-derived foam cells, which was dependent on concomitant oxidative stress because the antioxidant N-acetylcysteine inhibited the lipid accumulation. Collectively, our results indicate that exposure to MWCNT is associated with accelerated progression of atherosclerosis, which could be related to both increased adherence of monocytes onto the endothelium and oxidative stress-mediated transformation of monocytes to foam cells.

Ultrafine carbon particles induce interleukin-8 gene transcription and p38 MAPK activation in normal human bronchial epithelial cells.

Epidemiological studies suggest that ultrafine particles contribute to particulate matter-induced adverse health effects. Interleukin (IL)-8 is an important proinflammatory cytokine in the human lung that is induced in respiratory cells exposed to a variety of environmental insults, including ambient air ultrafine particles. In this study, we examined the effect of a model ultrafine particle on IL-8 expression and the cellular mechanisms responsible for this event. Here, we report that carbonaceous ultrafine particles consisting of synthetic elemental carbon particles (UfCP) markedly increase the expression of IL-8 mRNA and protein in normal human bronchial epithelial (NHBE) cells. IL-8 promoter activity was increased by UfCP exposure in NHBE cells, indicating UfCP-induced IL-8 expression is transcriptionally regulated. IL-8 expression in NHBE is known to be regulated by nuclear factor (NF)-kappaB activation. However, UfCP did not induce inhibitory factor kappaBalpha degradation, NF-kappaB-DNA binding, or NF-kappaB-dependent promoter activity in NHBE cells, indicating that UfCP induces IL-8 expression through a mechanism that is independent of NF-kappaB activation. Additionally, we observed that UfCP exposure induces the phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) in a biphasic manner and that the inhibition of p38 MAPK activity can block IL-8 mRNA expression induced by UfCP in NHBE cells. These results demonstrate that UfCP-induced expression of IL-8 involves a transcriptional mechanism and activation of p38 MAPK in NHBE cells.