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Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation

Gliotoxin (GTX) is the major and the most potent mycotoxin that is secreted by Aspergillus fumigatus, which is capable of injuring and killing microglial cells, astrocytes, and oligodendrocytes. During the last years, studies with patients and experimental models of multiple sclerosis (MS), which is...

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Autores principales: Fraga-Silva, Thais Fernanda de Campos, Mimura, Luiza Ayumi Nishiyama, Leite, Laysla de Campos Toledo, Borim, Patrícia Aparecida, Ishikawa, Larissa Lumi Watanabe, Venturini, James, de Arruda, Maria Sueli Parreira, Sartori, Alexandrina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722733/
https://www.ncbi.nlm.nih.gov/pubmed/31357414
http://dx.doi.org/10.3390/toxins11080443
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author Fraga-Silva, Thais Fernanda de Campos
Mimura, Luiza Ayumi Nishiyama
Leite, Laysla de Campos Toledo
Borim, Patrícia Aparecida
Ishikawa, Larissa Lumi Watanabe
Venturini, James
de Arruda, Maria Sueli Parreira
Sartori, Alexandrina
author_facet Fraga-Silva, Thais Fernanda de Campos
Mimura, Luiza Ayumi Nishiyama
Leite, Laysla de Campos Toledo
Borim, Patrícia Aparecida
Ishikawa, Larissa Lumi Watanabe
Venturini, James
de Arruda, Maria Sueli Parreira
Sartori, Alexandrina
author_sort Fraga-Silva, Thais Fernanda de Campos
collection PubMed
description Gliotoxin (GTX) is the major and the most potent mycotoxin that is secreted by Aspergillus fumigatus, which is capable of injuring and killing microglial cells, astrocytes, and oligodendrocytes. During the last years, studies with patients and experimental models of multiple sclerosis (MS), which is an autoimmune disease of the central nervous system (CNS), suggested that fungal infections are among the possible initiators or aggravators of this pathology. The deleterious effect can occur through a direct interaction of the fungus with the CNS or by the toxin release from a non-neurological site. In the present work, we investigated the effect of GTX on experimental autoimmune encephalomyelitis (EAE) development. Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein and then intraperitoneally injected with three doses of GTX (1 mg/kg b.w., each) on days 4, 7, and 10. GTX aggravated clinical symptoms of the disease in a dose-dependent way and this outcome was concomitant with an increased neuroinflammation. CNS analyses revealed that GTX locally increased the relative expression of inflammatory genes and the cytokine production. Our results indicate that GTX administered in a non-neuronal site was able to increase neuroinflammation in EAE. Other mycotoxins could also be deleterious to many neurological diseases by similar mechanisms.
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spelling pubmed-67227332019-09-10 Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation Fraga-Silva, Thais Fernanda de Campos Mimura, Luiza Ayumi Nishiyama Leite, Laysla de Campos Toledo Borim, Patrícia Aparecida Ishikawa, Larissa Lumi Watanabe Venturini, James de Arruda, Maria Sueli Parreira Sartori, Alexandrina Toxins (Basel) Article Gliotoxin (GTX) is the major and the most potent mycotoxin that is secreted by Aspergillus fumigatus, which is capable of injuring and killing microglial cells, astrocytes, and oligodendrocytes. During the last years, studies with patients and experimental models of multiple sclerosis (MS), which is an autoimmune disease of the central nervous system (CNS), suggested that fungal infections are among the possible initiators or aggravators of this pathology. The deleterious effect can occur through a direct interaction of the fungus with the CNS or by the toxin release from a non-neurological site. In the present work, we investigated the effect of GTX on experimental autoimmune encephalomyelitis (EAE) development. Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein and then intraperitoneally injected with three doses of GTX (1 mg/kg b.w., each) on days 4, 7, and 10. GTX aggravated clinical symptoms of the disease in a dose-dependent way and this outcome was concomitant with an increased neuroinflammation. CNS analyses revealed that GTX locally increased the relative expression of inflammatory genes and the cytokine production. Our results indicate that GTX administered in a non-neuronal site was able to increase neuroinflammation in EAE. Other mycotoxins could also be deleterious to many neurological diseases by similar mechanisms. MDPI 2019-07-26 /pmc/articles/PMC6722733/ /pubmed/31357414 http://dx.doi.org/10.3390/toxins11080443 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fraga-Silva, Thais Fernanda de Campos
Mimura, Luiza Ayumi Nishiyama
Leite, Laysla de Campos Toledo
Borim, Patrícia Aparecida
Ishikawa, Larissa Lumi Watanabe
Venturini, James
de Arruda, Maria Sueli Parreira
Sartori, Alexandrina
Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation
title Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation
title_full Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation
title_fullStr Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation
title_full_unstemmed Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation
title_short Gliotoxin Aggravates Experimental Autoimmune Encephalomyelitis by Triggering Neuroinflammation
title_sort gliotoxin aggravates experimental autoimmune encephalomyelitis by triggering neuroinflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722733/
https://www.ncbi.nlm.nih.gov/pubmed/31357414
http://dx.doi.org/10.3390/toxins11080443
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