Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles
Inflammatory mechanisms triggered by microglial cells are involved in the pathophysiology of several brain disorders, hindering repair. Herein, we propose the use of retinoic acid-loaded polymeric nanoparticles (RA-NP) as a means to modulate microglia response towards an anti-inflammatory and neurop...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/6742427 |
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| _version_ | 1832562794328752128 |
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| author | Marta Machado-Pereira Tiago Santos Lino Ferreira Liliana Bernardino Raquel Ferreira |
| author_facet | Marta Machado-Pereira Tiago Santos Lino Ferreira Liliana Bernardino Raquel Ferreira |
| author_sort | Marta Machado-Pereira |
| collection | DOAJ |
| description | Inflammatory mechanisms triggered by microglial cells are involved in the pathophysiology of several brain disorders, hindering repair. Herein, we propose the use of retinoic acid-loaded polymeric nanoparticles (RA-NP) as a means to modulate microglia response towards an anti-inflammatory and neuroprotective phenotype (M2). RA-NP were first confirmed to be internalized by N9 microglial cells; nanoparticles did not affect cell survival at concentrations below 100 μg/mL. Then, immunocytochemical studies were performed to assess the expression of pro- and anti-inflammatory mediators. Our results show that RA-NP inhibited LPS-induced release of nitric oxide and the expression of inducible nitric oxide synthase and promoted arginase-1 and interleukin-4 production. Additionally, RA-NP induced a ramified microglia morphology (indicative of M2 state), promoting tissue viability, particularly neuronal survival, and restored the expression of postsynaptic protein-95 in organotypic hippocampal slice cultures exposed to an inflammatory challenge. RA-NP also proved to be more efficient than the free equivalent RA concentration. Altogether, our data indicate that RA-NP may be envisioned as a promising therapeutic agent for brain inflammatory diseases. |
| format | Article |
| id | doaj-art-227b3bb63cf042ed84517e1c4fb2ecbb |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-227b3bb63cf042ed84517e1c4fb2ecbb2025-02-03T01:21:48ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/67424276742427Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded NanoparticlesMarta Machado-Pereira0Tiago Santos1Lino Ferreira2Liliana Bernardino3Raquel Ferreira4Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marquês d’Ávila e Bolama, 6201-001 Covilhã, PortugalHealth Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marquês d’Ávila e Bolama, 6201-001 Covilhã, PortugalCenter for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, PortugalHealth Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marquês d’Ávila e Bolama, 6201-001 Covilhã, PortugalHealth Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marquês d’Ávila e Bolama, 6201-001 Covilhã, PortugalInflammatory mechanisms triggered by microglial cells are involved in the pathophysiology of several brain disorders, hindering repair. Herein, we propose the use of retinoic acid-loaded polymeric nanoparticles (RA-NP) as a means to modulate microglia response towards an anti-inflammatory and neuroprotective phenotype (M2). RA-NP were first confirmed to be internalized by N9 microglial cells; nanoparticles did not affect cell survival at concentrations below 100 μg/mL. Then, immunocytochemical studies were performed to assess the expression of pro- and anti-inflammatory mediators. Our results show that RA-NP inhibited LPS-induced release of nitric oxide and the expression of inducible nitric oxide synthase and promoted arginase-1 and interleukin-4 production. Additionally, RA-NP induced a ramified microglia morphology (indicative of M2 state), promoting tissue viability, particularly neuronal survival, and restored the expression of postsynaptic protein-95 in organotypic hippocampal slice cultures exposed to an inflammatory challenge. RA-NP also proved to be more efficient than the free equivalent RA concentration. Altogether, our data indicate that RA-NP may be envisioned as a promising therapeutic agent for brain inflammatory diseases.http://dx.doi.org/10.1155/2017/6742427 |
| spellingShingle | Marta Machado-Pereira Tiago Santos Lino Ferreira Liliana Bernardino Raquel Ferreira Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles Mediators of Inflammation |
| title | Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles |
| title_full | Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles |
| title_fullStr | Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles |
| title_full_unstemmed | Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles |
| title_short | Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles |
| title_sort | anti inflammatory strategy for m2 microglial polarization using retinoic acid loaded nanoparticles |
| url | http://dx.doi.org/10.1155/2017/6742427 |
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