PMID- 30763585 OWN - NLM STAT- MEDLINE DCOM- 20200526 LR - 20201210 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 376 IP - 2 DP - 2019 Mar 15 TI - Lipopolysaccharide mediates time-dependent macrophage M1/M2 polarization through the Tim-3/Galectin-9 signalling pathway. PG - 124-132 LID - S0014-4827(19)30053-9 [pii] LID - 10.1016/j.yexcr.2019.02.007 [doi] AB - Macrophages are dynamic cells whose phenotypes and functions are regulated by surrounding inflammatory mediators after pathogenic infection. Imbalanced polarization of classically activated (M1) and alternatively activated (M2) macrophages is closely associated with infection-related complications and their severity. The pathway of T-cell immunoglobulin mucin 3 (Tim-3)/galectin-9 (Gal-9) plays an important role in infection by regulating macrophage function. However, the effects of Tim-3/Gal-9 signalling on M1/M2 macrophage polarization are unclear. Bone marrow-derived macrophages (BMDMs) were stimulated with 0.1 mug/mL lipopolysaccharide (LPS). M1/M2 phenotypic macrophage markers were measured 0, 1, 3, 6, 12, and 24 h after stimulation, alpha-lactose was used to inhibit Gal-9, anti-mouse Tim-3 antibody was used to block Tim-3, recombinant mouse-Gal-9 (rm-Gal-9) was used to activate Tim-3, which were aimed to verify the role of the Tim-3/Gal-9 pathway in the balance of M1/M2 macrophages when stimulated with LPS. Short-term LPS stimulation upregulated Gal-9 expression and secretion, enhanced the association between Gal-9 and Tim-3, and activated the Tim-3/Gal-9 signalling pathway, eventually inhibiting M1 polarization. Long-term stimulation downregulated Gal-9 expression and secretion, reduced the association between Gal-9 and Tim-3, and inhibited the Tim-3/Gal-9 signalling pathway, eventually promoting M1 polarization, however, decreased M2 polarization and Gal-9 autocrine functions. Overall, LPS had a biphasic effect on BMDMs polarization through the Tim-3/Gal-9 pathway, which was time-dependent. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Zhang, Wang AU - Zhang W AD - Department of Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China. FAU - Zhang, Yuntao AU - Zhang Y AD - Department of Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China. Electronic address: zyticu@zju.edu.cn. FAU - He, Yuxian AU - He Y AD - Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China. FAU - Wang, Xiying AU - Wang X AD - Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China. FAU - Fang, Qiang AU - Fang Q AD - Department of Critical Care Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China. Electronic address: 1183005@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190211 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Galectins) RN - 0 (Havcr2 protein, mouse) RN - 0 (Hepatitis A Virus Cellular Receptor 2) RN - 0 (Lipopolysaccharides) RN - 0 (galectin 9, mouse) SB - IM MH - Acute Lung Injury/immunology MH - Animals MH - Bone Marrow Cells/immunology MH - *Cell Polarity MH - Cells, Cultured MH - Galectins/*metabolism MH - Hepatitis A Virus Cellular Receptor 2/*metabolism MH - Lipopolysaccharides/*immunology MH - *Macrophage Activation MH - Macrophages/cytology/*immunology/metabolism MH - Mice, Inbred C57BL MH - Respiratory Distress Syndrome/immunology MH - *Signal Transduction MH - Time OTO - NOTNLM OT - Galectin-9 OT - Lipopolysaccharide OT - Macrophages OT - Polarization OT - Tim-3 EDAT- 2019/02/15 06:00 MHDA- 2020/05/27 06:00 CRDT- 2019/02/15 06:00 PHST- 2018/11/15 00:00 [received] PHST- 2019/02/09 00:00 [accepted] PHST- 2019/02/15 06:00 [pubmed] PHST- 2020/05/27 06:00 [medline] PHST- 2019/02/15 06:00 [entrez] AID - S0014-4827(19)30053-9 [pii] AID - 10.1016/j.yexcr.2019.02.007 [doi] PST - ppublish SO - Exp Cell Res. 2019 Mar 15;376(2):124-132. doi: 10.1016/j.yexcr.2019.02.007. Epub 2019 Feb 11.