title: Proteomic profiling of dextran sulfate sodium induced acute ulcerative colitis mice serum exosomes and their immunomodulatory impact on macrophages.
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.
authors.affiliation: Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong S.A.R., China.
authors.forename: Wing-Yan
authors.initials: WY
authors.lastname: Wong
authors.affiliation: Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong S.A.R., China.
authors.forename: Magnolia Muk-Lan
authors.initials: MM
authors.lastname: Lee
authors.affiliation: Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong S.A.R., China.
authors.forename: Brandon Dow
authors.initials: BD
authors.lastname: Chan
authors.affiliation: Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R., China.
authors.forename: Richard Kin-Tin
authors.initials: RK
authors.lastname: Kam
authors.affiliation: Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong S.A.R., China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong S.A.R., China.|Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong S.A.R., China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Lu
authors.affiliation: Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong S.A.R., China.
authors.forename: William Chi-Shing
authors.initials: WC
authors.lastname: Tai
mesh_terms: D000818:Animals; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism*; D003167:Complement Activation; D016264:Dextran Sulfate / Q000009:adverse effects*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D055354:Exosomes / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D040901:Proteomics
chemical_list: D020543:Proteome; D016264:Dextran Sulfate
keywords: 2DE; Acute colitis; Animal proteomics; Dextran sulfate sodium; Macrophages; Serum exosomes