ReferenceID 2988
Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway
Front Immunol
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 t
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Record Fields
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- Reference Id
- 2988
- Evidence Id
- 19578
- Core Evidence Id
- 19578
- Source Reference Id
- 5978
- Herb2 Reference Id
- HBREF006775
- Subject Paper Key
- HBIN046423_33868286
- Pubmed Id
- 33868286
- Doi
- 10.3389/fimmu.2021.649463
- Paper Title
- Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway
- Paper Abstract
- 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 IFNgamma stimulated macrophages. At the molecular level, tiliroside facilitated the proteasomal degradation of HIF-1alpha and downregulated mRNA expressions of HIF-1alpha 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.
- Journal
- Front Immunol
- Publish Year
- 2021
- Experiment Subject
- mouse; ifngamma stimulated macrophages; m1 and m2 macrophages
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Ulcerative Colitis; Metabolic Disorders; Inflammation; Colitis
- Paper Title Cn
- Paper Title En
- Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway
- Bilingual Status
- semi_complete