Effects of urban particulate matter with high glucose on human monocytes U937. Issue 4 (14th July 2015)

• Record Type: Journal Article
• Authors: Zhang, Yue; Mo, Yiqun; Gu, Aihua; Wan, Rong; Zhang, Qunwei; Tollerud, David J.
• Is Part Of: Journal of applied toxicology. Volume 36:Issue 4(2016)
• Page Start: 586
• Page End: 595
• Publication Date: 2015-07-14
• Subjects: particulate matter -- diabetes mellitus -- high glucose -- oxidative stress -- MMP‐2 -- MMP‐9 -- monocytes -- p38 phosphorylation; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3198
• Languages: English
• ISSNs: 0260-437X

Abstract

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. Copyright © 2015 John Wiley & Sons, Ltd. Abstract : This study examined the effects of urban particulate matter (U‐PM) with or without high glucose on human monocytes U937. The results showed that exposure of monocytes to U‐PM alone caused ROS generation, increased p38 phosphorylation, up‐regulation of MMP‐2, MMP‐9 and proinflammatory cytokines IL‐1β and IL‐8, and increased activity of pro‐MMP‐2 and pro‐MMP‐9. These effects were enhanced significantly when cells were exposed to U‐PM with high glucose. Our findings have important implications in understanding the health effects of PM on diabetics.