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Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells
BACKGROUND: Microglia play key roles in innate immunity, homeostasis, and neurotropic support in the central nervous system. Similar to macrophages, microglia adopt two different activation phenotypes, the classical and alternative activation. Resolvin D1 (RvD1) is considered to display potent anti-...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983859/ https://www.ncbi.nlm.nih.gov/pubmed/24708771 http://dx.doi.org/10.1186/1742-2094-11-72 |
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author | Li, Longyan Wu, Yan Wang, Yanping Wu, Jing Song, Limin Xian, Wenjing Yuan, Shiying Pei, Lei Shang, You |
author_facet | Li, Longyan Wu, Yan Wang, Yanping Wu, Jing Song, Limin Xian, Wenjing Yuan, Shiying Pei, Lei Shang, You |
author_sort | Li, Longyan |
collection | PubMed |
description | BACKGROUND: Microglia play key roles in innate immunity, homeostasis, and neurotropic support in the central nervous system. Similar to macrophages, microglia adopt two different activation phenotypes, the classical and alternative activation. Resolvin D1 (RvD1) is considered to display potent anti-inflammatory and pro-resolving actions in inflammatory models. In this present study, we investigate the effect of RvD1 on IL-4-induced alternative activation in murine BV-2 microglial cells. METHODS: BV-2 cells were incubated with RvD1 alone, IL-4 alone, or the combination of RvD1 and IL-4. Western blot and immunofluorescence were performed to detect protein levels of alternative activation markers arginase 1 (Arg1), chitinase 3-like 3 (Ym1). Moreover, we investigated the effects of RvD1 on IL-4-induced activation of signal transducer and activators of transcription 6 (STAT6) and peroxisome proliferator-activated receptor gamma (PPARγ). RESULTS: RvD1 promoted IL-4-induced microglia alternative activation by increasing the expression of Arg1 and Ym1. RvD1 also enhanced phosphorylation of STAT6, nuclear translocation of PPARγ and the DNA binding activity of STAT6 and PPARγ. These effects were reversed by butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (a formyl peptide receptor 2 antagonist). Further, the effects of RvD1 and IL-4 on Arg1 and Ym1 were blocked by the application of leflunomide (a STAT6 inhibitor) or GW9662 (a PPARγ antagonist). CONCLUSIONS: Our studies demonstrate that RvD1 promotes IL-4-induced alternative activation via STAT6 and PPARγ signaling pathways in microglia. These findings suggest that RvD1 may have therapeutic potential for neuroinflammatory diseases. |
format | Online Article Text |
id | pubmed-3983859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39838592014-04-12 Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells Li, Longyan Wu, Yan Wang, Yanping Wu, Jing Song, Limin Xian, Wenjing Yuan, Shiying Pei, Lei Shang, You J Neuroinflammation Research BACKGROUND: Microglia play key roles in innate immunity, homeostasis, and neurotropic support in the central nervous system. Similar to macrophages, microglia adopt two different activation phenotypes, the classical and alternative activation. Resolvin D1 (RvD1) is considered to display potent anti-inflammatory and pro-resolving actions in inflammatory models. In this present study, we investigate the effect of RvD1 on IL-4-induced alternative activation in murine BV-2 microglial cells. METHODS: BV-2 cells were incubated with RvD1 alone, IL-4 alone, or the combination of RvD1 and IL-4. Western blot and immunofluorescence were performed to detect protein levels of alternative activation markers arginase 1 (Arg1), chitinase 3-like 3 (Ym1). Moreover, we investigated the effects of RvD1 on IL-4-induced activation of signal transducer and activators of transcription 6 (STAT6) and peroxisome proliferator-activated receptor gamma (PPARγ). RESULTS: RvD1 promoted IL-4-induced microglia alternative activation by increasing the expression of Arg1 and Ym1. RvD1 also enhanced phosphorylation of STAT6, nuclear translocation of PPARγ and the DNA binding activity of STAT6 and PPARγ. These effects were reversed by butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (a formyl peptide receptor 2 antagonist). Further, the effects of RvD1 and IL-4 on Arg1 and Ym1 were blocked by the application of leflunomide (a STAT6 inhibitor) or GW9662 (a PPARγ antagonist). CONCLUSIONS: Our studies demonstrate that RvD1 promotes IL-4-induced alternative activation via STAT6 and PPARγ signaling pathways in microglia. These findings suggest that RvD1 may have therapeutic potential for neuroinflammatory diseases. BioMed Central 2014-04-05 /pmc/articles/PMC3983859/ /pubmed/24708771 http://dx.doi.org/10.1186/1742-2094-11-72 Text en Copyright © 2014 Li et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Li, Longyan Wu, Yan Wang, Yanping Wu, Jing Song, Limin Xian, Wenjing Yuan, Shiying Pei, Lei Shang, You Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells |
title | Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells |
title_full | Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells |
title_fullStr | Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells |
title_full_unstemmed | Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells |
title_short | Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells |
title_sort | resolvin d1 promotes the interleukin-4-induced alternative activation in bv-2 microglial cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983859/ https://www.ncbi.nlm.nih.gov/pubmed/24708771 http://dx.doi.org/10.1186/1742-2094-11-72 |
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