Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles
Oxyresveratrol, a stilbene extracted from the plant <i>Artocarpus lakoocha</i> Roxb., has been reported to provide a considerable anti-inflammatory activity. Since the mechanisms of this therapeutic action have been poorly clarified, we investigated whether oxyresveratrol affects the rel...
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MDPI AG
2021-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/8/2106 |
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| author | Salvatore Calogero Gaglio Marta Donini Piyachat Evelyn Denbaes Stefano Dusi Massimiliano Perduca |
| author_facet | Salvatore Calogero Gaglio Marta Donini Piyachat Evelyn Denbaes Stefano Dusi Massimiliano Perduca |
| author_sort | Salvatore Calogero Gaglio |
| collection | DOAJ |
| description | Oxyresveratrol, a stilbene extracted from the plant <i>Artocarpus lakoocha</i> Roxb., has been reported to provide a considerable anti-inflammatory activity. Since the mechanisms of this therapeutic action have been poorly clarified, we investigated whether oxyresveratrol affects the release of the pro-inflammatory cytokines IL-12, IL-6, and TNF-α by human dendritic cells (DCs). We found that oxyresveratrol did not elicit per se the release of these cytokines, but inhibited their secretion induced upon DC stimulation with R848 (Resiquimod), a well-known immune cell activator engaging receptors recognizing RNA viruses. We then investigated whether the inclusion of oxyresveratrol into nanoparticles promoting its ingestion by DCs could favor its effects on cytokine release. For this purpose we synthesized and characterized poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and we assessed their effects on DCs. We found that bare PLGA nanoparticles did not affect cytokine secretion by resting DCs, but increased IL-12, IL-6, and TNF-α secretion by R848-stimulated DCs, an event known as “priming effect”. We then loaded PLGA nanoparticles with oxyresveratrol and we observed that oxyresveratrol-bearing particles did not stimulate the cytokine release by resting DCs and inhibited the PLGA-dependent enhancement of IL-12, IL-6, and TNF-α secretion by R848-stimulated DCs. The results herein reported indicate that oxyresveratrol suppresses the cytokine production by activated DCs, thus representing a good anti-inflammatory and immune-suppressive agent. Moreover, its inclusion into PLGA nanoparticles mitigates the pro-inflammatory effects due to cooperation between nanoparticles and R848 in cytokine release. Therefore, oxyresveratrol can be able to contrast the synergistic effects of nanoparticles with microorganisms that could be present in the patient tissues, therefore overcoming a condition unfavorable to the use of some nanoparticles in biological systems. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:33:58Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8efc7a76daef4c0ba255db484e85d7a62023-11-21T14:27:18ZengMDPI AGMolecules1420-30492021-04-01268210610.3390/molecules26082106Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA NanoparticlesSalvatore Calogero Gaglio0Marta Donini1Piyachat Evelyn Denbaes2Stefano Dusi3Massimiliano Perduca4Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona, ItalyDepartment of Medicine, Section of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, ItalyDepartment of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona, ItalyDepartment of Medicine, Section of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, ItalyDepartment of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona, ItalyOxyresveratrol, a stilbene extracted from the plant <i>Artocarpus lakoocha</i> Roxb., has been reported to provide a considerable anti-inflammatory activity. Since the mechanisms of this therapeutic action have been poorly clarified, we investigated whether oxyresveratrol affects the release of the pro-inflammatory cytokines IL-12, IL-6, and TNF-α by human dendritic cells (DCs). We found that oxyresveratrol did not elicit per se the release of these cytokines, but inhibited their secretion induced upon DC stimulation with R848 (Resiquimod), a well-known immune cell activator engaging receptors recognizing RNA viruses. We then investigated whether the inclusion of oxyresveratrol into nanoparticles promoting its ingestion by DCs could favor its effects on cytokine release. For this purpose we synthesized and characterized poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and we assessed their effects on DCs. We found that bare PLGA nanoparticles did not affect cytokine secretion by resting DCs, but increased IL-12, IL-6, and TNF-α secretion by R848-stimulated DCs, an event known as “priming effect”. We then loaded PLGA nanoparticles with oxyresveratrol and we observed that oxyresveratrol-bearing particles did not stimulate the cytokine release by resting DCs and inhibited the PLGA-dependent enhancement of IL-12, IL-6, and TNF-α secretion by R848-stimulated DCs. The results herein reported indicate that oxyresveratrol suppresses the cytokine production by activated DCs, thus representing a good anti-inflammatory and immune-suppressive agent. Moreover, its inclusion into PLGA nanoparticles mitigates the pro-inflammatory effects due to cooperation between nanoparticles and R848 in cytokine release. Therefore, oxyresveratrol can be able to contrast the synergistic effects of nanoparticles with microorganisms that could be present in the patient tissues, therefore overcoming a condition unfavorable to the use of some nanoparticles in biological systems.https://www.mdpi.com/1420-3049/26/8/2106dendritic cellsoxyresveratrolcytokinesPLGA nanoparticlesinflammation |
| spellingShingle | Salvatore Calogero Gaglio Marta Donini Piyachat Evelyn Denbaes Stefano Dusi Massimiliano Perduca Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles Molecules dendritic cells oxyresveratrol cytokines PLGA nanoparticles inflammation |
| title | Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles |
| title_full | Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles |
| title_fullStr | Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles |
| title_full_unstemmed | Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles |
| title_short | Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles |
| title_sort | oxyresveratrol inhibits r848 induced pro inflammatory mediators release by human dendritic cells even when embedded in plga nanoparticles |
| topic | dendritic cells oxyresveratrol cytokines PLGA nanoparticles inflammation |
| url | https://www.mdpi.com/1420-3049/26/8/2106 |
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