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β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice

Context: β-Sitosterol (BS), the primary constituent of plants and vegetables, exhibits multiple biological effects. Objective: This study explores its effect of immune-regulation on macrophages and its potential for rheumatoid arthritis (RA) therapy. Materials and methods:In vitro, bone marrow-deriv...

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Autores principales: Liu, Rui, Hao, Donglin, Xu, Wenya, Li, Jinjin, Li, Xiaoru, Shen, Dong, Sheng, Kang, Zhao, Lin, Xu, Weiwei, Gao, Zhongen, Zhao, Xu, Liu, Qiuhong, Zhang, Yiting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442231/
https://www.ncbi.nlm.nih.gov/pubmed/30905278
http://dx.doi.org/10.1080/13880209.2019.1577461
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author Liu, Rui
Hao, Donglin
Xu, Wenya
Li, Jinjin
Li, Xiaoru
Shen, Dong
Sheng, Kang
Zhao, Lin
Xu, Weiwei
Gao, Zhongen
Zhao, Xu
Liu, Qiuhong
Zhang, Yiting
author_facet Liu, Rui
Hao, Donglin
Xu, Wenya
Li, Jinjin
Li, Xiaoru
Shen, Dong
Sheng, Kang
Zhao, Lin
Xu, Weiwei
Gao, Zhongen
Zhao, Xu
Liu, Qiuhong
Zhang, Yiting
author_sort Liu, Rui
collection PubMed
description Context: β-Sitosterol (BS), the primary constituent of plants and vegetables, exhibits multiple biological effects. Objective: This study explores its effect of immune-regulation on macrophages and its potential for rheumatoid arthritis (RA) therapy. Materials and methods:In vitro, bone marrow-derived macrophages (BMDMs) were treated with 5, 25 and 50 μM BS in the M1 or M2 polarization conditions. In vivo, either i.p. injection with 20 or 50 mg/kg BS every 2 d after boost immunization of collagen-induced arthritis (CIA) or adoptive transfer of 2 × 10(6) BS-treated BMDMs (BS-BMDMs) at the day before CIA were adopted in mice to test the therapeutic effect. IL-10 antibody depletion was used in the period of above treatments to discuss the underlying mechanism. Results: The phenotypes and function of BMDMs showed that 5, 25 and 50 μM BS significantly repressed the M1 polarization and augmented M2 polarization dependent upon concentration. The expression of iNOS, IL-1β, CD86 and MHCII in 25 μM BS-treated M1-polarized BMDMs was reduced by 50.2, 47.1, 87.1 and 31.3%, respectively. In contrast, the expression of arginase-1, IL-10, CD163 and CD206 in 25 μM BS-treated M2-polarized BMDMs was increased by 65.6, 107.4, 23.5 and 51.3%, respectively. In CIA mice, either i.p. injection with BS or adoptive transfer of BS-BMDMs could alleviate the symptoms of ankle swelling (vehicle group: 3.13 ± 0.102 mm; 20 mg/kg BS group: 2.64 ± 0.043 mm; 50 mg/kg BS group: 2.36 ± 0.084 mm; BMDMs group: 3.09 ± 0.174 mm; BS-BMDMs group: 2.43 ± 0.042 mm), reduce the levels of collagen-specific antibodies (IgG and IgG1, but not IgG2c, p < 0.05) and inhibit the production of pro-inflammatory cytokines (p < 0.05). Depletion of IL-10 counteracted the effect of BS treatment (α-IL-10 vs. RatIgG1, p < 0.01 on day 16), highlighting the role of IL-10 in the anti-inflammatory response. Conclusions: These results suggested that BS could modulate the functions of macrophages and might be a promising agent for RA therapy.
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spelling pubmed-64422312019-04-04 β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice Liu, Rui Hao, Donglin Xu, Wenya Li, Jinjin Li, Xiaoru Shen, Dong Sheng, Kang Zhao, Lin Xu, Weiwei Gao, Zhongen Zhao, Xu Liu, Qiuhong Zhang, Yiting Pharm Biol Research Article Context: β-Sitosterol (BS), the primary constituent of plants and vegetables, exhibits multiple biological effects. Objective: This study explores its effect of immune-regulation on macrophages and its potential for rheumatoid arthritis (RA) therapy. Materials and methods:In vitro, bone marrow-derived macrophages (BMDMs) were treated with 5, 25 and 50 μM BS in the M1 or M2 polarization conditions. In vivo, either i.p. injection with 20 or 50 mg/kg BS every 2 d after boost immunization of collagen-induced arthritis (CIA) or adoptive transfer of 2 × 10(6) BS-treated BMDMs (BS-BMDMs) at the day before CIA were adopted in mice to test the therapeutic effect. IL-10 antibody depletion was used in the period of above treatments to discuss the underlying mechanism. Results: The phenotypes and function of BMDMs showed that 5, 25 and 50 μM BS significantly repressed the M1 polarization and augmented M2 polarization dependent upon concentration. The expression of iNOS, IL-1β, CD86 and MHCII in 25 μM BS-treated M1-polarized BMDMs was reduced by 50.2, 47.1, 87.1 and 31.3%, respectively. In contrast, the expression of arginase-1, IL-10, CD163 and CD206 in 25 μM BS-treated M2-polarized BMDMs was increased by 65.6, 107.4, 23.5 and 51.3%, respectively. In CIA mice, either i.p. injection with BS or adoptive transfer of BS-BMDMs could alleviate the symptoms of ankle swelling (vehicle group: 3.13 ± 0.102 mm; 20 mg/kg BS group: 2.64 ± 0.043 mm; 50 mg/kg BS group: 2.36 ± 0.084 mm; BMDMs group: 3.09 ± 0.174 mm; BS-BMDMs group: 2.43 ± 0.042 mm), reduce the levels of collagen-specific antibodies (IgG and IgG1, but not IgG2c, p < 0.05) and inhibit the production of pro-inflammatory cytokines (p < 0.05). Depletion of IL-10 counteracted the effect of BS treatment (α-IL-10 vs. RatIgG1, p < 0.01 on day 16), highlighting the role of IL-10 in the anti-inflammatory response. Conclusions: These results suggested that BS could modulate the functions of macrophages and might be a promising agent for RA therapy. Taylor & Francis 2019-03-24 /pmc/articles/PMC6442231/ /pubmed/30905278 http://dx.doi.org/10.1080/13880209.2019.1577461 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 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 cited.
spellingShingle Research Article
Liu, Rui
Hao, Donglin
Xu, Wenya
Li, Jinjin
Li, Xiaoru
Shen, Dong
Sheng, Kang
Zhao, Lin
Xu, Weiwei
Gao, Zhongen
Zhao, Xu
Liu, Qiuhong
Zhang, Yiting
β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice
title β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice
title_full β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice
title_fullStr β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice
title_full_unstemmed β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice
title_short β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice
title_sort β-sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442231/
https://www.ncbi.nlm.nih.gov/pubmed/30905278
http://dx.doi.org/10.1080/13880209.2019.1577461
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