Lycium barbarum Polysaccharide Antagonizes LPS-Induced Inflammation by Altering the Glycolysis and Differentiation of Macrophages by Triggering the Degradation of PKM2
Autor: | Jing-Jing Wang, Tao Feng, Huan Ding, Xiao-Ya Zhang, Lei Yin |
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Rok vydání: | 2021 |
Předmět: |
Lipopolysaccharides
0301 basic medicine Nedd4 Ubiquitin Protein Ligases Pyruvate Kinase Pharmaceutical Science Inflammation PKM2 Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Ubiquitin GTP-Binding Proteins medicine Animals Lactic Acid Pharmacology biology Chemistry Kinase Ubiquitination Cell Differentiation General Medicine Cell biology Glucose RAW 264.7 Cells 030104 developmental biology Hypoxia-inducible factors 030220 oncology & carcinogenesis Proteolysis biology.protein Tumor necrosis factor alpha medicine.symptom Glycolysis Pyruvate kinase Drugs Chinese Herbal |
Zdroj: | Biological and Pharmaceutical Bulletin. 44:379-388 |
ISSN: | 1347-5215 0918-6158 |
Popis: | Lipopolysaccharide (LPS)-induced inflammation is the leading cause of multiple organ failure in sepsis. Pyruvate kinase 2 (PKM2) is a protein kinase and transcriptional coactivator that plays an important role in glycolysis. Recent studies have confirmed that glycolysis maintains the M1 differentiation and induces immune activation in macrophages. Lycium barbarum polysaccharide (LBP), the main bioactive component of Chinese wolfberry, suppresses glycolysis and inflammation. Here, RAW264.7 macrophages were treated with LBP for evaluating its effects against LPS-induced inflammation. The differentiation of M1/M2 macrophages was assessed by flow cytometry for assessing the cell surface markers, CD86 and CD206. The enrichment of hypoxia inducible factor (HIF)-1α and ubiquitin in the PKM2 protein complex was determined by co-immunoprecipitation. LBP suppressed LPS-induced glycolysis, differentiation of M1 macrophages, and the production of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and high mobility group (HMG) 1 proteins. The suppressive effects of LBP were similar to those of PKM2 knockdown, but were abolished by the overexpression of PKM2. LPS elevated the mRNA and protein levels of PKM2. LBP reduced the LPS-induced expression of PKM2 protein, but had no effects on the expression of PKM2 mRNA. LPS inhibited the ubiquitination of PKM2, probably by downregulating the expression of ubiquitin ligases, including Nedd4L, Nedd4, and Gnb2. LBP interfered with the inhibition of PKM2 ubiquitination by upregulating the expression of Nedd4L, Nedd4, and Gnb2. In conclusion, LBP suppressed the LPS-induced inflammation by altering glycolysis and the M1 differentiation of macrophages. The effects of LBP were mediated by the downregulation of PKM2 via enhanced ubiquitination. |
Databáze: | OpenAIRE |
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