PMID- 31918287 OWN - NLM STAT- MEDLINE DCOM- 20200929 LR - 20200929 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 122 DP - 2020 Feb TI - Immunosuppressive Siglec-E ligands on mouse aorta are up-regulated by LPS via NF-kappaB pathway. PG - 109760 LID - S0753-3322(19)35382-X [pii] LID - 10.1016/j.biopha.2019.109760 [doi] AB - AIMS: Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor. Both Siglec-E and Siglec-9 are primarily found on neutrophils, macrophages, and monocytes. When Siglec-E binds to sialoglycan ligands in its extracellular environment, it halts the immune cells' inflammatory responses. In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta. METHODS: The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified. In vivo, the expression of Siglec-E ligands was detected after LPS treatment, with or without NF-kappaB inhibitor administration. In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-kappaB inhibitors. MAECs induced by LPS were co-cultured with macrophages and the effect of increased expression of Siglec-E ligands analyzed. RESULTS: Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro. In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-kappaB signaling pathway dependent manner. In MAECs, the expression of Siglec-E ligands was also increased by LPS via an NF-kappaB signaling pathway. Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS. Notably, co-incubation of macrophages with LPS-treated MAECs induced macrophage apoptosis and decreased macrophage phagocytosis, effects that were completely reversed by blocking Siglec-E binding to Siglec-E ligands. CONCLUSIONS: These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation. CI - Copyright (c) 2019 The Author(s). Published by Elsevier Masson SAS.. All rights reserved. FAU - Liu, Hongmei AU - Liu H AD - Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, ChongQing 400038, China. FAU - Zheng, Yu AU - Zheng Y AD - Department of Pharmacy, Hainan Western Central Hospital, Danzhou, Hainan 571799, China. FAU - Zhang, Yingxian AU - Zhang Y AD - Department of Pharmacy, Third Affiliated Hospital, ChongQing Medical University, Chongqing 401120, China. FAU - Li, Jin AU - Li J AD - Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, ChongQing 400038, China. FAU - Fernandes, Steve M AU - Fernandes SM AD - Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. FAU - Zeng, Dongfeng AU - Zeng D AD - Department of Haematology, Daping Hospital, Army Medical University, ChongQing, 400042, China. FAU - Li, Xiaohui AU - Li X AD - Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, ChongQing 400038, China. FAU - Schnaar, Ronald L AU - Schnaar RL AD - Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: Schnaar@jhu.edu. FAU - Jia, Yi AU - Jia Y AD - Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, ChongQing 400038, China. Electronic address: jy@tmmu.edu.cn. LA - eng PT - Journal Article DEP - 20191230 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, B-Lymphocyte) RN - 0 (Immunosuppressive Agents) RN - 0 (Ligands) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Sialic Acid Binding Immunoglobulin-like Lectins) RN - 0 (Siglece protein, mouse) SB - IM MH - Animals MH - Antigens, CD/*metabolism MH - Antigens, Differentiation, B-Lymphocyte/*metabolism MH - Aorta/drug effects/metabolism MH - Endothelial Cells/drug effects/metabolism MH - Escherichia coli/drug effects MH - Immunosuppressive Agents/*pharmacology MH - Inflammation/drug therapy/metabolism MH - Ligands MH - Lipopolysaccharides/*pharmacology MH - Macrophages/drug effects/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Monocytes/drug effects/metabolism MH - NF-kappa B/*metabolism MH - Sialic Acid Binding Immunoglobulin-like Lectins/*metabolism MH - Signal Transduction/*drug effects/physiology MH - Transcriptional Activation/drug effects MH - Up-Regulation/*drug effects OTO - NOTNLM OT - Deleted in malignant brain tumors-1 OT - Endothelial cells OT - Inflammation OT - LPS OT - Siglec-E ligands EDAT- 2020/01/10 06:00 MHDA- 2020/09/30 06:00 CRDT- 2020/01/10 06:00 PHST- 2019/10/01 00:00 [received] PHST- 2019/12/02 00:00 [revised] PHST- 2019/12/04 00:00 [accepted] PHST- 2020/01/10 06:00 [pubmed] PHST- 2020/09/30 06:00 [medline] PHST- 2020/01/10 06:00 [entrez] AID - S0753-3322(19)35382-X [pii] AID - 10.1016/j.biopha.2019.109760 [doi] PST - ppublish SO - Biomed Pharmacother. 2020 Feb;122:109760. doi: 10.1016/j.biopha.2019.109760. Epub 2019 Dec 30.