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Murine Experimental Autoimmune Encephalomyelitis Is Diminished by Treatment with the Angiogenesis Inhibitors B20-4.1.1 and Angiostatin (K1-3)

Angiogenesis is the formation of new blood vessels form pre-existing vasculature whose contribution to inflammatory conditions of the Central Nervous System is being studied in order to generate novel therapeutic targets. This study is the first to investigate the impact of two particular angiogenes...

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Autores principales: MacMillan, Carolyn J., Doucette, Carolyn D., Warford, Jordan, Furlong, Suzanne J., Hoskin, David W., Easton, Alexander S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935931/
https://www.ncbi.nlm.nih.gov/pubmed/24587024
http://dx.doi.org/10.1371/journal.pone.0089770
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author MacMillan, Carolyn J.
Doucette, Carolyn D.
Warford, Jordan
Furlong, Suzanne J.
Hoskin, David W.
Easton, Alexander S.
author_facet MacMillan, Carolyn J.
Doucette, Carolyn D.
Warford, Jordan
Furlong, Suzanne J.
Hoskin, David W.
Easton, Alexander S.
author_sort MacMillan, Carolyn J.
collection PubMed
description Angiogenesis is the formation of new blood vessels form pre-existing vasculature whose contribution to inflammatory conditions of the Central Nervous System is being studied in order to generate novel therapeutic targets. This study is the first to investigate the impact of two particular angiogenesis inhibitors on murine Experimental Autoimmune Encephalomyelitis (EAE), an inflammatory disease that mimics aspects of the human disease Multiple Sclerosis. The inhibitors were chosen to reduce angiogenesis by complimentary means. Extrinsic factors were targeted with B20-4.1.1 through its ability to bind to murine Vascular Endothelial Growth Factor (VEGF). Vascular processes connected to angiogenesis were targeted directly with K(1-3), the first three kringle domains of angiostatin. Mice treated with B20-4.1.1 and K(1-3) from onset of signs had reduced clinical scores 18–21 days after EAE induction. Both agents suppressed spinal cord angiogenesis without effect on local VEGF expression. B20-4.1.1 reduced spinal cord vascular permeability while K(1-3) had no effect. T cell infiltration into the spinal cord at day 21 was unaffected by either treatment. B20-4.1.1 reduced peripheral T cell proliferation while K(1-3) had no effect. Lymphoid cells from treated mice produced reduced levels of the T helper-17 (Th-17) cell cytokine interleukin (IL)-17 with no effect on the Th-1 cytokine interferon (IFN)-γ or Th-2 cytokine IL-4. However, when both drugs were added in vitro to naive T cells or to antigen stimulated T cells from mice with untreated EAE they had no effect on proliferation or levels of IL-17 or IFN-γ. We conclude that these angiogenesis inhibitors mitigate EAE by both suppressing spinal cord angiogenesis and reducing peripheral T cell activation.
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spelling pubmed-39359312014-03-04 Murine Experimental Autoimmune Encephalomyelitis Is Diminished by Treatment with the Angiogenesis Inhibitors B20-4.1.1 and Angiostatin (K1-3) MacMillan, Carolyn J. Doucette, Carolyn D. Warford, Jordan Furlong, Suzanne J. Hoskin, David W. Easton, Alexander S. PLoS One Research Article Angiogenesis is the formation of new blood vessels form pre-existing vasculature whose contribution to inflammatory conditions of the Central Nervous System is being studied in order to generate novel therapeutic targets. This study is the first to investigate the impact of two particular angiogenesis inhibitors on murine Experimental Autoimmune Encephalomyelitis (EAE), an inflammatory disease that mimics aspects of the human disease Multiple Sclerosis. The inhibitors were chosen to reduce angiogenesis by complimentary means. Extrinsic factors were targeted with B20-4.1.1 through its ability to bind to murine Vascular Endothelial Growth Factor (VEGF). Vascular processes connected to angiogenesis were targeted directly with K(1-3), the first three kringle domains of angiostatin. Mice treated with B20-4.1.1 and K(1-3) from onset of signs had reduced clinical scores 18–21 days after EAE induction. Both agents suppressed spinal cord angiogenesis without effect on local VEGF expression. B20-4.1.1 reduced spinal cord vascular permeability while K(1-3) had no effect. T cell infiltration into the spinal cord at day 21 was unaffected by either treatment. B20-4.1.1 reduced peripheral T cell proliferation while K(1-3) had no effect. Lymphoid cells from treated mice produced reduced levels of the T helper-17 (Th-17) cell cytokine interleukin (IL)-17 with no effect on the Th-1 cytokine interferon (IFN)-γ or Th-2 cytokine IL-4. However, when both drugs were added in vitro to naive T cells or to antigen stimulated T cells from mice with untreated EAE they had no effect on proliferation or levels of IL-17 or IFN-γ. We conclude that these angiogenesis inhibitors mitigate EAE by both suppressing spinal cord angiogenesis and reducing peripheral T cell activation. Public Library of Science 2014-02-26 /pmc/articles/PMC3935931/ /pubmed/24587024 http://dx.doi.org/10.1371/journal.pone.0089770 Text en © 2014 MacMillan 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
MacMillan, Carolyn J.
Doucette, Carolyn D.
Warford, Jordan
Furlong, Suzanne J.
Hoskin, David W.
Easton, Alexander S.
Murine Experimental Autoimmune Encephalomyelitis Is Diminished by Treatment with the Angiogenesis Inhibitors B20-4.1.1 and Angiostatin (K1-3)
title Murine Experimental Autoimmune Encephalomyelitis Is Diminished by Treatment with the Angiogenesis Inhibitors B20-4.1.1 and Angiostatin (K1-3)
title_full Murine Experimental Autoimmune Encephalomyelitis Is Diminished by Treatment with the Angiogenesis Inhibitors B20-4.1.1 and Angiostatin (K1-3)
title_fullStr Murine Experimental Autoimmune Encephalomyelitis Is Diminished by Treatment with the Angiogenesis Inhibitors B20-4.1.1 and Angiostatin (K1-3)
title_full_unstemmed Murine Experimental Autoimmune Encephalomyelitis Is Diminished by Treatment with the Angiogenesis Inhibitors B20-4.1.1 and Angiostatin (K1-3)
title_short Murine Experimental Autoimmune Encephalomyelitis Is Diminished by Treatment with the Angiogenesis Inhibitors B20-4.1.1 and Angiostatin (K1-3)
title_sort murine experimental autoimmune encephalomyelitis is diminished by treatment with the angiogenesis inhibitors b20-4.1.1 and angiostatin (k1-3)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935931/
https://www.ncbi.nlm.nih.gov/pubmed/24587024
http://dx.doi.org/10.1371/journal.pone.0089770
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