Igg Plasma Cells Initiate Changes In The Protein C System In Mouse Ulcerative Colitis Through Cd14(+)Cd64(+) Macrophage Activation
ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE(2019)
摘要
Background. Inhibition of the protein (system (PCS) might be one of the mechanisms of ulcerative colitis (UC).Objectives. The aim of the study was to explore the role of IgG plasma cells in changes in the PCS in UC.Material and methods. Dextran sulfate sodium (DSS) was chosen to induce mouse UC. Inflammation was assessed using hematoxylin & eosin (H&E) staining and immunofluorescence. The profiling of colonic plasma cells and macrophages from colitis mice was analyzed with flow cytometry. After stimulation of macrophages with IgG type immune complex (IgG-IC), western blot was used to determine tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) protein levels. After co-incubation of colonic mucosa microvascular endothelial cells (MVECs) with TNF-alpha or IL-6, mitogen-activated protein kinase (MAPK) expression was detected.Results. The DSS-colitis mice showed higher inflammatory indexes (p < 0.05 or p < 0.01), accompanied by greater infiltration of CD38(+)IgG(+) plasma cells (p < 0.01), CD14(+)CD64(+) macrophages (p < 0.01) and IgG-IC than healthy mice. Enhancement of TNF-alpha and IL-6 protein expression was demonstrated in this subset of macrophages when stimulated by IgG-IC (p < 0.01). After MVECs were incubated with TNF-alpha or IL-6, the expression of beta-arrestin1, pP38 MAPK and AK MAPK exhibited an increase (p < 0.05 or p < 0.01), but downregulation of endothelial protein C receptor (EPCR) expression was observed (p < 0.05 or p < 0.01); this inhibition of EPCR expression was reversed by SB203580, SP600125 or U0126 (p < 0.05 or p < 0.01). In addition, changes in activated protein C (APC) presented results similar to those for EPCR expression (p < 0.05 or p < 0.01).Conclusions. These results reveal that the PCS is inhibited during UC processing. There is a possibility that the interaction between IgG plasma cells and CD14(+)CD64(+) macrophages, as well as further secretion of cytokines from CD14(+)CD64(+) macrophages by the formation and stimulation of IgG-IC, subsequently influence MVECs through the beta-arrestin-MAPK pathway. Enhancement of PCS activity may represent a novel approach for treating UC.
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关键词
macrophages,ulcerative colitis,MAPK,protein C system,plasma cells
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