Journal
JOURNAL OF APPLIED TOXICOLOGY
Volume 36, Issue 1, Pages 48-59Publisher
WILEY
DOI: 10.1002/jat.3143
Keywords
PM2; 5; oxidative stress; adhesion factor; ERK; AKT; NF-kappa B; reactive oxygen species; EA; hy926 cells
Categories
Funding
- National Natural Science Foundation of China [21377127, 11275264, U1432245]
- CAS/SAFEA International Partnership Program for Creative Research Teams
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The aim of this study was to explore the intracellular mechanisms underlying the cardiovascular toxicity of air particulate matter (PM) with an aerodynamic diameter of less than 2.5 mu m (PM2.5) in a human umbilical vein cell line, EA.hy926. We found that PM2.5 exposure triggered reactive oxygen species (ROS) generation, resulting in a significant decrease in cell viability. Data from Western blots showed that PM2.5 induced phosphorylation of Jun N-terminal kinase (JNK), extracellular signal regulatory kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and protein kinase B (AKT), and activation of nuclear factor kappa B (NF-B). We further observed a significant increase in expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) in a time- and dose-dependent manner. Moreover, the adhesion of monocytic THP-1 cells to EA.hy926 cells was greatly enhanced in the presence of PM2.5. However, N-acetylcysteine (NAC), a scavenger of ROS, prevented the increase of ROS generation, attenuated the phosphorylation of the above kinases, and decreased the NF-B activation as well as the expression of ICAM-1 and VCAM-1. Furthermore, ERK inhibitor (U0126), AKT inhibitor (LY294002) and NF-B inhibitor (BAY11-7082) significantly down-regulated PM2.5-induced ICAM-1 and VCAM-1 expression as well as adhesion of THP-1 cells, but not JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580), indicating that ERK/AKT/NF-B is involved in the signaling pathway that leads to PM2.5-induced ICAM-1 and VCAM-1 expression. These findings suggest PM2.5-induced ROS may function as signaling molecules triggering ICAM-1 and VCAM-1 expressions through activating the ERK/AKT/NF-B-dependent pathway, and further promoting monocyte adhesion to endothelial cells. Copyright (c) 2015 John Wiley & Sons, Ltd. We explored the underlying mechanisms of PM2.5-induced endothelial dysfucntion in EA.hy926 cells. PM2.5 exposure triggered reactive oxygen species (ROS) generation, phosphorylation of Jun N-terminal kinase (JNK), extracellular signal regulatory kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase B (AKT), activation of nuclear factor kappa B (NF-B), and increase in expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) as well as adhesion of THP-1 cells. However, ERK, AKT and NF-B inhibitors significantly down-regulated PM2.5-induced ICAM-1 and VCAM-1 expression, but not JNK inhibitor and p38 MAPK inhibitor. The results suggest that PM2.5-induced ROS trigger ICAM-1 and VCAM-1 expressions via activation of ERK/AKT/NF-B pathway.
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