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Dysfunctional endothelial-derived microparticles promote inflammatory macrophage formation via NF-?B and IL-1? signal pathways.

ABSTRACT: BACKGROUND:Circulating endothelial-derived microparticles (EMPs) are reported to be increased in acute coronary syndrome (ACS). However, it remains unclear whether EMPs from dysfunctional endothelium participate in the initiation and progression of ACS and what the underlying mechanisms might be. METHODS:Plasma EMPs were measured in 22 patients with ACS and 20 control patients without coronary artery diseases. EMPs from dysfunctional human umbilical vein endothelial cells (HUVECs) stressed by serum-starvation or hypoxia were compared to the EMPs from healthy HUVECs. Confocal and fluorescent microscopy was used to visualize the incorporation of EMPs into monocytes and the translocation of NF-?B. Monocyte adhesion, cell proliferation, and phagocytosis were detected by PKH26 red fluorescent labelling, Ki67 immunostaining, and Sudan IV staining for uptake of oxidized low-density lipoprotein, respectively. RESULTS:Plasma EMPs was significantly increased in ACS patients compared to controls. EMPs were incorporated into monocytes and EMPs from stressed HUVECs produced more pro-inflammatory cytokines compared to vehicle control, which was depended on NF-?B and IL-1? signal pathways. EMPs from dysfunctional endothelium promoted monocyte adherence via NF-?B and IL-1?-mediated MCP-1 and CCR-5 signals, as well as proliferation via the NF-?B and IL-1?-mediated Cyclin D1 signals. Finally, EMPs from dysfunctional endothelium showed greater promotion of macrophage phagocytosis forming foam cells to produce more pro-inflammatory cytokines. CONCLUSION:MPs might be involved in the inflammatory process in patients with ACS via NF-?B and IL-1?-dependent signals. Targeting EMP-mediated inflammatory responses may be a promising therapeutic strategy to limit the progression of disease in ACS.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6307808 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Dysfunctional endothelial-derived microparticles promote inflammatory macrophage formation via NF-кB and IL-1β signal pathways.

Wang Yanfang Y Liu Jie J Chen Xiaoli X Sun Huimin H Peng Sheng S Kuang Yashu Y Pi Jingjiang J Zhuang Tao T Zhang Lin L Yu Zuoren Z Tomlinson Brain B Chan Paul P Chen Yihan Y Zhang Yuzhen Y Li Ying Y

Journal of cellular and molecular medicine 20181018 1

<h4>Background</h4>Circulating endothelial-derived microparticles (EMPs) are reported to be increased in acute coronary syndrome (ACS). However, it remains unclear whether EMPs from dysfunctional endothelium participate in the initiation and progression of ACS and what the underlying mechanisms might be.<h4>Methods</h4>Plasma EMPs were measured in 22 patients with ACS and 20 control patients without coronary artery diseases. EMPs from dysfunctional human umbilical vein endothelial cells (HUVECs) ...[more]

PMID: 30334371

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Project description:Decompression sickness is a systemic pathophysiological process caused by bubbles and endothelial microparticles (EMPs) are established markers reflecting competency of endothelial function and vascular biology. Here, we investigated the effects of bubble-induced EMPs on endothelial cells in vitro and vivo. Rat pulmonary microvascular endothelial cells (PMVECs) were isolated and stimulated by bubbles and bubble-induced EMPs were collected and incubated with normal PMVECs in vitro. Cell viability and apoptosis were detected using Cell Counting Kit-8 assay and Annexin V FITC/PI double staining, respectively. Cell permeability and pro-inflammatory cytokines were determined by electric cell substrate impedance sensing and enzyme-linked immunosorbent assay, respectively. Intracellular nitric oxide and reactive oxygen species production were analyzed microscopically. In vivo study, bubble-induced EMPs were intravenously injected to the rats and soluble thrombomodulin, intercellular adhesion molecule 1, and vascullar adhesion molecule 1 were involved in evaluating endothelial dysfunction. In our study, bubble stimulus resulted in a significant increase of EMPs release by 3 fold. Bubble-induced EMPs significantly decreased cell viability and increased cell apoptosis. Moreover, bubble-induced EMPs induced abnormal increase of cell permeability and over-expression of pro-inflammatory cytokines. Intracellular ROS production increased while NO production decreased. These negative effects caused by bubble-induced EMPs were remarkably suppressed when EMPs pretreated with surfactant FSN-100. Finally, intravenous injection of bubble-induced EMPs caused elevations of soluble thrombomodulin and pro-inflammatory cytokines in the circulation. Altogether, our results demonstrated that bubble-induced EMPs can mediate endothelial dysfunction in vitro and vivo, which can be attenuated by EMPs abatement strategy. These data expanded our horizon of the detrimental effects of bubble-induced EMPs, which may be of great concern in DCS.

Project description:Background:Metabolic syndrome is characterized by macrophage infiltration and inflammatory responses-metaflammation in adipose tissue. IL-6 and IL-1? could mediate the inflammatory responses in macrophage stimulated-preadipocytes by modulating MAPK and NF-?B pathways. To test this hypothesis we used antibodies to block IL-6 and IL-1? action in macrophage conditioned medium (MacCM)-stimulated human white preadipocytes. Moreover, as interventions that prevent this could potentially be used to treat or prevent metabolic syndrome, and 1?,25(OH)2D3 has previously been reported to exert an anti-inflammatory action on macrophage-stimulated adipocytes, in this study we also investigated whether 1?,25(OH)2D3 could attenuate inflammatory responses in MacCM-stimulated preadipocytes, and explored the potential anti-inflammatory mechanisms. Methods:Human white preadipocytes were cultured with 25% MacCM for 24 h to elicit inflammatory responses. This was confirmed by measuring the concentrations and mRNA levels of major pro-inflammatory factors [IL-1?, IL-6, IL-8, monocyte chemoattractant protein (MCP)-1 and regulated on activation, normal T cell expressed and secreted (RANTES)] by ELISA and qPCR, respectively. IL-6 and IL-1? actions were blocked using IL-6 antibody (300 ng/ml) and IL-1? antibody (15 ?g/ml), respectively. Potential anti-inflammatory effects of 1?,25(OH)2D3 were investigated by pre-treatment and treatment of 1?,25(OH)2D3 (0.01 to 10 nM) for 48 h in MacCM-stimulated preadipocytes. In parallel, western blotting was used to determine inflammatory signaling molecules including relA of the NF-?B pathway and p44/42 MAPK modified during these processes. Results:MacCM enhanced the secretion and gene expression of IL-1?, IL-6, IL-8, MCP-1 and RANTES by increasing the phosphorylation levels of relA and p44/42 MAPK in preadipocytes, whereas blocking IL-6 and IL-1? action inhibited the inflammatory responses by decreasing p44/42 MAPK and relA phosphorylation, respectively. Furthermore, 10 nM of 1?,25(OH)2D3 generally inhibited the IL-6 and IL-1?-mediated inflammatory responses, and reduced both p44/42 MAPK and relA phosphorylation in MacCM-stimulated preadipocytes. Conclusions:1?,25(OH)2D3 attenuates IL-6 and IL-1?-mediated inflammatory responses, probably by inhibiting p44/42 MAPK and relA phosphorylation in MacCM-stimulated human white preadipocytes.

Dataset Information

Dysfunctional endothelial-derived microparticles promote inflammatory macrophage formation via NF-?B and IL-1? signal pathways.

Publications

Dysfunctional endothelial-derived microparticles promote inflammatory macrophage formation via NF-кB and IL-1β signal pathways.

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