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Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway
Macrophages polarized to different phenotypes critically contribute to colitis development by coordinating inflammatory and anti-inflammatory processes. Herein, targeting the balance between the pro-inflammatory M1 and the anti-inflammatory M2 macrophage phenotypes can be a novel therapeutic approac...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044352/ https://www.ncbi.nlm.nih.gov/pubmed/33868286 http://dx.doi.org/10.3389/fimmu.2021.649463 |
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author | Zhuang, Hongda Lv, Qi Zhong, Chao Cui, Yaru He, Luling Zhang, Cheng Yu, Jun |
author_facet | Zhuang, Hongda Lv, Qi Zhong, Chao Cui, Yaru He, Luling Zhang, Cheng Yu, Jun |
author_sort | Zhuang, Hongda |
collection | PubMed |
description | Macrophages polarized to different phenotypes critically contribute to colitis development by coordinating inflammatory and anti-inflammatory processes. Herein, targeting the balance between the pro-inflammatory M1 and the anti-inflammatory M2 macrophage phenotypes can be a novel therapeutic approach for colitis. In the present study, we firstly demonstrated that tiliroside possessed the ability to alleviate the clinical symptoms of colitis as evidenced by decreased disease activity index (DAI) scores, longer colon length, reduced myeloperoxidase (MPO) activity, and improvement of colonic pathological damage in vivo. Furthermore, we showed that tiliroside modulated the balance between M1 and M2 macrophages toward a more anti-inflammatory status in colonic lamina propria but has little effect on the T cell population and epithelial barrier function in colitis mice. The macrophage depletion study further showed the protective effect of tiliroside was macrophage dependent in vivo. Mechanistically, our study demonstrated that tiliroside regulated cellular metabolism by inhibiting aerobic glycolysis in LPS and IFNγ stimulated macrophages. At the molecular level, tiliroside facilitated the proteasomal degradation of HIF-1α and downregulated mRNA expressions of HIF-1α dependent glycolytic enzymes in macrophages. Collectively, our data highlight the aberrant M1/M2 macrophage polarization in the initiation and development of ulcerative colitis and put forth the stage for considering tiliroside as a metabolic regulator in reprogramming macrophage polarization, which may serve as a promising therapeutic approach for treatment of inflammation-associated and metabolic disorders. |
format | Online Article Text |
id | pubmed-8044352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80443522021-04-15 Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway Zhuang, Hongda Lv, Qi Zhong, Chao Cui, Yaru He, Luling Zhang, Cheng Yu, Jun Front Immunol Immunology Macrophages polarized to different phenotypes critically contribute to colitis development by coordinating inflammatory and anti-inflammatory processes. Herein, targeting the balance between the pro-inflammatory M1 and the anti-inflammatory M2 macrophage phenotypes can be a novel therapeutic approach for colitis. In the present study, we firstly demonstrated that tiliroside possessed the ability to alleviate the clinical symptoms of colitis as evidenced by decreased disease activity index (DAI) scores, longer colon length, reduced myeloperoxidase (MPO) activity, and improvement of colonic pathological damage in vivo. Furthermore, we showed that tiliroside modulated the balance between M1 and M2 macrophages toward a more anti-inflammatory status in colonic lamina propria but has little effect on the T cell population and epithelial barrier function in colitis mice. The macrophage depletion study further showed the protective effect of tiliroside was macrophage dependent in vivo. Mechanistically, our study demonstrated that tiliroside regulated cellular metabolism by inhibiting aerobic glycolysis in LPS and IFNγ stimulated macrophages. At the molecular level, tiliroside facilitated the proteasomal degradation of HIF-1α and downregulated mRNA expressions of HIF-1α dependent glycolytic enzymes in macrophages. Collectively, our data highlight the aberrant M1/M2 macrophage polarization in the initiation and development of ulcerative colitis and put forth the stage for considering tiliroside as a metabolic regulator in reprogramming macrophage polarization, which may serve as a promising therapeutic approach for treatment of inflammation-associated and metabolic disorders. Frontiers Media S.A. 2021-03-31 /pmc/articles/PMC8044352/ /pubmed/33868286 http://dx.doi.org/10.3389/fimmu.2021.649463 Text en Copyright © 2021 Zhuang, Lv, Zhong, Cui, He, Zhang and Yu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zhuang, Hongda Lv, Qi Zhong, Chao Cui, Yaru He, Luling Zhang, Cheng Yu, Jun Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway |
title | Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway |
title_full | Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway |
title_fullStr | Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway |
title_full_unstemmed | Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway |
title_short | Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway |
title_sort | tiliroside ameliorates ulcerative colitis by restoring the m1/m2 macrophage balance via the hif-1α/glycolysis pathway |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044352/ https://www.ncbi.nlm.nih.gov/pubmed/33868286 http://dx.doi.org/10.3389/fimmu.2021.649463 |
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