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Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia

BACKGROUND: Silica nanoparticles (SiNPs) are being formulated for cellular imaging and for nonviral gene delivery in the central nervous system (CNS), but it is unclear what potential effects SiNPs can elicit once they enter the CNS. As the resident macrophages of the CNS, microglia are the cells mo...

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Autores principales: Choi, Judy, Zheng, Qingdong, Katz, Howard E., Guilarte, Tomás R.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866671/
https://www.ncbi.nlm.nih.gov/pubmed/20439179
http://dx.doi.org/10.1289/ehp.0901534
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author Choi, Judy
Zheng, Qingdong
Katz, Howard E.
Guilarte, Tomás R.
author_facet Choi, Judy
Zheng, Qingdong
Katz, Howard E.
Guilarte, Tomás R.
author_sort Choi, Judy
collection PubMed
description BACKGROUND: Silica nanoparticles (SiNPs) are being formulated for cellular imaging and for nonviral gene delivery in the central nervous system (CNS), but it is unclear what potential effects SiNPs can elicit once they enter the CNS. As the resident macrophages of the CNS, microglia are the cells most likely to respond to SiNP entry into the brain. Upon activation, they are capable of undergoing morphological and functional changes. OBJECTIVE: We examined the effects of SiNP exposure using primary rat microglia. METHODS: We observed microglial uptake of SiNPs using transmission electron and fluorescence confocal microscopy. Microglial functions, including phagocytosis, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), expression of proinflammatory genes, and cytokine release, were measured after SiNP exposure at different concentrations. RESULTS: Microglia are capable of avidly taking up SiNPs at all concentrations tested. These same concentrations did not elicit cytotoxicity or a change in phagocytic activity. SiNPs did increase the productions of both intracellular ROS and RNS. We also observed a significant decrease in tumor necrosis factor-α gene expression at all concentrations tested and a significant increase in COX-2 (cyclooxygenase-2) gene expression at the highest concentration of SiNPs. Analysis of cytokine release showed a detectable level of interleukin-1β. CONCLUSIONS: This is the first study demonstrating the in vitro effects of SiNPs in primary microglia. Our findings suggest that very low levels of SiNPs are capable of altering microglial function. Increased ROS and RNS production, changes in proinflammatory genes, and cytokine release may not only adversely affect microglial function but also affect surrounding neurons.
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spelling pubmed-28666712010-05-26 Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia Choi, Judy Zheng, Qingdong Katz, Howard E. Guilarte, Tomás R. Environ Health Perspect Research BACKGROUND: Silica nanoparticles (SiNPs) are being formulated for cellular imaging and for nonviral gene delivery in the central nervous system (CNS), but it is unclear what potential effects SiNPs can elicit once they enter the CNS. As the resident macrophages of the CNS, microglia are the cells most likely to respond to SiNP entry into the brain. Upon activation, they are capable of undergoing morphological and functional changes. OBJECTIVE: We examined the effects of SiNP exposure using primary rat microglia. METHODS: We observed microglial uptake of SiNPs using transmission electron and fluorescence confocal microscopy. Microglial functions, including phagocytosis, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), expression of proinflammatory genes, and cytokine release, were measured after SiNP exposure at different concentrations. RESULTS: Microglia are capable of avidly taking up SiNPs at all concentrations tested. These same concentrations did not elicit cytotoxicity or a change in phagocytic activity. SiNPs did increase the productions of both intracellular ROS and RNS. We also observed a significant decrease in tumor necrosis factor-α gene expression at all concentrations tested and a significant increase in COX-2 (cyclooxygenase-2) gene expression at the highest concentration of SiNPs. Analysis of cytokine release showed a detectable level of interleukin-1β. CONCLUSIONS: This is the first study demonstrating the in vitro effects of SiNPs in primary microglia. Our findings suggest that very low levels of SiNPs are capable of altering microglial function. Increased ROS and RNS production, changes in proinflammatory genes, and cytokine release may not only adversely affect microglial function but also affect surrounding neurons. National Institute of Environmental Health Sciences 2010-05 2009-12-21 /pmc/articles/PMC2866671/ /pubmed/20439179 http://dx.doi.org/10.1289/ehp.0901534 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Choi, Judy
Zheng, Qingdong
Katz, Howard E.
Guilarte, Tomás R.
Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia
title Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia
title_full Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia
title_fullStr Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia
title_full_unstemmed Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia
title_short Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia
title_sort silica-based nanoparticle uptake and cellular response by primary microglia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866671/
https://www.ncbi.nlm.nih.gov/pubmed/20439179
http://dx.doi.org/10.1289/ehp.0901534
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