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Dengue Virus Enhances Thrombomodulin and ICAM-1 Expression through the Macrophage Migration Inhibitory Factor Induction of the MAPK and PI3K Signaling Pathways
Dengue virus (DV) infections cause mild dengue fever (DF) or severe life-threatening dengue hemorrhagic fever (DHF). The mechanisms that cause hemorrhage in DV infections remain poorly understood. Thrombomodulin (TM) is a glycoprotein expressed on the surface of vascular endothelial cells that plays...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557271/ https://www.ncbi.nlm.nih.gov/pubmed/23383040 http://dx.doi.org/10.1371/journal.pone.0055018 |
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author | Yeh, Trai-Ming Liu, Shu-Hsiang Lin, Kao-Chang Kuo, Chieh Kuo, Shu-Yun Huang, Tzuu-Yuan Yen, Yong-Ren Wen, Rong-Kun Chen, Lien-Cheng Fu, Tsai-Feng |
author_facet | Yeh, Trai-Ming Liu, Shu-Hsiang Lin, Kao-Chang Kuo, Chieh Kuo, Shu-Yun Huang, Tzuu-Yuan Yen, Yong-Ren Wen, Rong-Kun Chen, Lien-Cheng Fu, Tsai-Feng |
author_sort | Yeh, Trai-Ming |
collection | PubMed |
description | Dengue virus (DV) infections cause mild dengue fever (DF) or severe life-threatening dengue hemorrhagic fever (DHF). The mechanisms that cause hemorrhage in DV infections remain poorly understood. Thrombomodulin (TM) is a glycoprotein expressed on the surface of vascular endothelial cells that plays an important role in the thrombin-mediated activation of protein C. Prior studies have shown that the serum levels of soluble TM (sTM) and macrophage migration inhibitory factor (MIF) are significantly increased in DHF patients compared to levels in DF patients or normal controls. In this study, we investigated how MIF and sTM concentrations are enhanced in the plasma of DHF patients and the potential effect of MIF on coagulation through its influence on two factors: thrombomodulin (TM) and intercellular adhesion molecule-1 (ICAM-1) in endothelial cells and monocytes. Recombinant human macrophage migration inhibitory factor (rMIF) was used to treat monocytic THP-1 cells and endothelial HMEC-1 cells or primary HUVEC cells. The subsequent expression of TM and ICAM-1 was assessed by immunofluorescent staining and flow cytometry analysis. Additionally, the co-incubation of THP-1 cells with various cell signaling pathway inhibitors was used to determine the pathways through which MIF mediated its effect. The data provided evidence that severe DV infections induce MIF expression, which in turn stimulates monocytes or endothelial cells to express TM and ICAM-1 via the Erk, JNK MAPK and the PI3K signaling pathways, supporting the idea that MIF may play an important role as a regulator of coagulation. |
format | Online Article Text |
id | pubmed-3557271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35572712013-02-04 Dengue Virus Enhances Thrombomodulin and ICAM-1 Expression through the Macrophage Migration Inhibitory Factor Induction of the MAPK and PI3K Signaling Pathways Yeh, Trai-Ming Liu, Shu-Hsiang Lin, Kao-Chang Kuo, Chieh Kuo, Shu-Yun Huang, Tzuu-Yuan Yen, Yong-Ren Wen, Rong-Kun Chen, Lien-Cheng Fu, Tsai-Feng PLoS One Research Article Dengue virus (DV) infections cause mild dengue fever (DF) or severe life-threatening dengue hemorrhagic fever (DHF). The mechanisms that cause hemorrhage in DV infections remain poorly understood. Thrombomodulin (TM) is a glycoprotein expressed on the surface of vascular endothelial cells that plays an important role in the thrombin-mediated activation of protein C. Prior studies have shown that the serum levels of soluble TM (sTM) and macrophage migration inhibitory factor (MIF) are significantly increased in DHF patients compared to levels in DF patients or normal controls. In this study, we investigated how MIF and sTM concentrations are enhanced in the plasma of DHF patients and the potential effect of MIF on coagulation through its influence on two factors: thrombomodulin (TM) and intercellular adhesion molecule-1 (ICAM-1) in endothelial cells and monocytes. Recombinant human macrophage migration inhibitory factor (rMIF) was used to treat monocytic THP-1 cells and endothelial HMEC-1 cells or primary HUVEC cells. The subsequent expression of TM and ICAM-1 was assessed by immunofluorescent staining and flow cytometry analysis. Additionally, the co-incubation of THP-1 cells with various cell signaling pathway inhibitors was used to determine the pathways through which MIF mediated its effect. The data provided evidence that severe DV infections induce MIF expression, which in turn stimulates monocytes or endothelial cells to express TM and ICAM-1 via the Erk, JNK MAPK and the PI3K signaling pathways, supporting the idea that MIF may play an important role as a regulator of coagulation. Public Library of Science 2013-01-28 /pmc/articles/PMC3557271/ /pubmed/23383040 http://dx.doi.org/10.1371/journal.pone.0055018 Text en © 2013 Yeh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yeh, Trai-Ming Liu, Shu-Hsiang Lin, Kao-Chang Kuo, Chieh Kuo, Shu-Yun Huang, Tzuu-Yuan Yen, Yong-Ren Wen, Rong-Kun Chen, Lien-Cheng Fu, Tsai-Feng Dengue Virus Enhances Thrombomodulin and ICAM-1 Expression through the Macrophage Migration Inhibitory Factor Induction of the MAPK and PI3K Signaling Pathways |
title | Dengue Virus Enhances Thrombomodulin and ICAM-1 Expression through the Macrophage Migration Inhibitory Factor Induction of the MAPK and PI3K Signaling Pathways |
title_full | Dengue Virus Enhances Thrombomodulin and ICAM-1 Expression through the Macrophage Migration Inhibitory Factor Induction of the MAPK and PI3K Signaling Pathways |
title_fullStr | Dengue Virus Enhances Thrombomodulin and ICAM-1 Expression through the Macrophage Migration Inhibitory Factor Induction of the MAPK and PI3K Signaling Pathways |
title_full_unstemmed | Dengue Virus Enhances Thrombomodulin and ICAM-1 Expression through the Macrophage Migration Inhibitory Factor Induction of the MAPK and PI3K Signaling Pathways |
title_short | Dengue Virus Enhances Thrombomodulin and ICAM-1 Expression through the Macrophage Migration Inhibitory Factor Induction of the MAPK and PI3K Signaling Pathways |
title_sort | dengue virus enhances thrombomodulin and icam-1 expression through the macrophage migration inhibitory factor induction of the mapk and pi3k signaling pathways |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557271/ https://www.ncbi.nlm.nih.gov/pubmed/23383040 http://dx.doi.org/10.1371/journal.pone.0055018 |
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