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Title: Proteomic profiling of dextran sulfate sodium induced acute ulcerative colitis mice serum exosomes and their immunomodulatory impact on macrophages
Authors: Wong, WY
Lee, MML
Chan, BD
Kam, RKT
Zhang, G
Lu, AP
Tai, WCS
Issue Date: 2016
Source: Proteomics, 2016, v. 16, no. 7, p. 1131-1145
Abstract: Macrophages are essential for the maintenance of intestinal homeostasis, and their activation has been proposed to be critical to the pathogenesis of inflammatory bowel disease (IBD). Although there are many recognized mediators of macrophage activation, increasing evidence suggests that macrophages respond to exosome stimulation. Exosomes are 40-150 nm microvesicles released from different cell types and are found in a variety of physiological fluids, including serum. As studies have shown that circulating exosomes participate in intercellular communication and can mediate the immune response, we hypothesized that exosomes may play a role in the pathogenesis of IBD though modulation of macrophage activity. In this study, we used the dextran sulfate sodium (DSS) induced acute colitis mice model to investigate the effect of serum exosomes on macrophages and identify exosome proteins potentially involved in macrophage activation. We treated RAW264.7 macrophages with serum exosomes isolated from dextran sulfate sodium induced mice and found that treatment induced phosphorylation of p38 and ERK and production of tumor necrosis factor α when compared to treatment with exosomes isolated from control mice. Subsequent proteomic analysis identified 56 differentially expressed proteins, a majority of which were acute-phase proteins and immunoglobulins. Bioinformatics analysis suggested these proteins were mainly involved in the complement and coagulation cascade, which has been implicated in macrophage activation. Our findings provide new insight into the role of circulating serum exosomes in acute colitis and contribute to the understanding of macrophage activation in the pathogenesis of IBD.
Keywords: 2DE
Acute colitis
Animal proteomics
Dextran sulfate sodium
Serum exosomes
Publisher: Wiley-VCH
Journal: Proteomics 
ISSN: 1615-9853
EISSN: 1615-9861
DOI: 10.1002/pmic.201500174
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