title: Effects of urban particulate matter with high glucose on human monocytes U937.
abstract: Epidemiological studies and animal experiments have shown that individuals with preexisting diseases, such as diabetes mellitus (DM), are more susceptible to particulate matter (PM)-related cardiovascular diseases. However, the underlying mechanisms are still unclear. We hypothesized that PM and high glucose combined would cause enhanced effects on activation of monocytes and p38 mitogen-activated protein kinase (MAPK) by inducing oxidative stress, which would further activate matrix metalloproteinases (MMPs). Human monocytes U937 were used to test the effects of urban particulate matter (U-PM) and high glucose. The results showed that exposure of monocytes to non-toxic doses of U-PM alone caused generation of reactive oxygen species (ROS), increased phosphorylation of p38, and activation of monocytes which was reflected by up-regulation of MMP-2, MMP-9 and proinflammatory cytokines IL-1β and IL-8 expression and increased activity of pro-MMP-2 and pro-MMP-9. These effects were enhanced significantly when cells were exposed to U-PM in a high-glucose environment. Our results also showed that pre-treatment of cells with ROS scavengers or inhibitors abolished U-PM and high glucose-induced increased phosphorylation of p38. Up-regulation of pro-MMP-2 and pro-MMP-9 activity by U-PM in the setting of high glucose level was dramatically attenuated by treatment of cells with the p38-specific inhibitor, SB203580. These results suggest that activation of MMPs by U-PM with high glucose is partly through p38 phosphorylation that is induced by oxidative stress. Our findings may have important implications in understanding the potential health effects of PM on susceptible populations such as those with DM.
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY, 40209, USA.|duPont Manual High School, 120 West Lee Street, Louisville, KY, 40208, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY, 40209, USA.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Mo
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gu
authors.affiliation: Department of Pathology, Fujian Medical University, Fujian, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY, 40209, USA.
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY, 40209, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Tollerud
mesh_terms: D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D007093:Imidazoles; D053583:Interleukin-1beta; D016209:Interleukin-8; D052638:Particulate Matter; D011725:Pyridines; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D018093:Gelatinases; C069860:progelatinase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D005947:Glucose; C093642:SB 203580
keywords: MMP-2; MMP-9; diabetes mellitus; high glucose; monocytes; oxidative stress; p38 phosphorylation; particulate matter