Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 8, August, p. 1101–1110

doi: 10.17219/acem/94160

Publication type: original article

Language: English

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IgG plasma cells initiate changes in the protein C system in mouse ulcerative colitis through CD14+CD64+ macrophage activation

Xu Hong Lin1,D, Hui Chao Wang2,B, Yong Yu Li3,E, Jun Ling Guo4,C, Yu Xia Li1,B, Guan Chang Cheng4,A, Dan Dan Wei1,F, Rui Lin Yang1,C, Jun Jie Zhang5,F, De Sheng Yang6,B, Bin Wang1,B, Xue Qun Ren5,A

1 Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital Affiliated to Henan University, Kaifeng, China

2 Department of Nephrology, First Affiliated Hospital of Henan University, Kaifeng, China

3 Department of Pathophysiology, Tongji University School of Medicine, Shanghai, China

4 Department of Cardiovascular Medicine, Huaihe Hospital Affiliated to Henan University, Kaifeng, China

5 Department of General Surgery, Huaihe Hospital Affiliated to Henan University, Kaifeng, China

6 Department of Gastroenterology, Huaihe Hospital Affiliated to Henan University, Kaifeng, China

Abstract

Background. Inhibition of the protein C 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 α (TNF-α) and interleukin 6 (IL-6) protein levels. After co-incubation of colonic mucosa microvascular endothelial cells (MVECs) with TNF-α 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-α 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-α or IL-6, the expression of β-arrestin1, pP38 MAPK and pJNK 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).
Conclusion. 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 β-arrestin-MAPK pathway. Enhancement of PCS activity may represent a novel approach for treating UC.

Key words

macrophages, ulcerative colitis, MAPK, protein C system, plasma cells

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