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Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in cli...

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Autores principales: Bozic, Iva, Savic, Danijela, Jovanovic, Marija, Bjelobaba, Ivana, Laketa, Danijela, Nedeljkovic, Nadezda, Stojiljkovic, Mirjana, Pekovic, Sanja, Lavrnja, Irena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564589/
https://www.ncbi.nlm.nih.gov/pubmed/26413464
http://dx.doi.org/10.1155/2015/923614
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author Bozic, Iva
Savic, Danijela
Jovanovic, Marija
Bjelobaba, Ivana
Laketa, Danijela
Nedeljkovic, Nadezda
Stojiljkovic, Mirjana
Pekovic, Sanja
Lavrnja, Irena
author_facet Bozic, Iva
Savic, Danijela
Jovanovic, Marija
Bjelobaba, Ivana
Laketa, Danijela
Nedeljkovic, Nadezda
Stojiljkovic, Mirjana
Pekovic, Sanja
Lavrnja, Irena
author_sort Bozic, Iva
collection PubMed
description Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation.
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spelling pubmed-45645892015-09-27 Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase Bozic, Iva Savic, Danijela Jovanovic, Marija Bjelobaba, Ivana Laketa, Danijela Nedeljkovic, Nadezda Stojiljkovic, Mirjana Pekovic, Sanja Lavrnja, Irena Anal Cell Pathol (Amst) Research Article Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation. Hindawi Publishing Corporation 2015 2015-08-27 /pmc/articles/PMC4564589/ /pubmed/26413464 http://dx.doi.org/10.1155/2015/923614 Text en Copyright © 2015 Iva Bozic et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bozic, Iva
Savic, Danijela
Jovanovic, Marija
Bjelobaba, Ivana
Laketa, Danijela
Nedeljkovic, Nadezda
Stojiljkovic, Mirjana
Pekovic, Sanja
Lavrnja, Irena
Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase
title Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase
title_full Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase
title_fullStr Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase
title_full_unstemmed Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase
title_short Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase
title_sort low-dose ribavirin treatments attenuate neuroinflammatory activation of bv-2 cells by interfering with inducible nitric oxide synthase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564589/
https://www.ncbi.nlm.nih.gov/pubmed/26413464
http://dx.doi.org/10.1155/2015/923614
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