ArticleStem cell research & therapy2022
TNFα and IFNγ rapidly activate PI3K-AKT signaling to drive glycolysis that confers mesenchymal stem cells enhanced anti-inflammatory property.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 80 citations in OpenAlex.
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- Network Pharmacology, Molecular Docking and Dynamics Simulation Reveal the Anti-Colitis Mechanism ofClinical and experimental gastroenterology · 2026Article
- Application of Human Umbilical Cord Mesenchymal Stem Cells and Their Derived Exosomes in Gastrointestinal Diseases.International journal of nanomedicine · 2026Review
- Comparative Transcriptomic Profiling of Mesenchymal Stem Cells from Distinct Tissue Origins and Isolation Methods Highlights the Stability and Immunomodulatory Signature of Umbilical Cord-Derived Smumf Cells.Tissue engineering and regenerative medicine · 2026Article
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- Targeting the double-edged sword: cytokines in the pathogenesis and treatment of autoimmune diseases.Inflammopharmacology · 2025Review
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- Environmental pollutant Di-(2-ethylhexyl) phthalate induces asthenozoospermia: new insights from network toxicology.Molecular diversity · 2025Article
- METTL1-mediated mCell death & disease · 2025Article
- The role of cytokine licensing in shaping the therapeutic potential of wharton's jelly MSCs: metabolic shift towards immunomodulation at the expense of differentiation.Stem cell research & therapy · 2025Article
- Protect Effects of Perilla Seed Extract and Its Active Ingredient Luteolin Against Inflammatory Bowel Disease Model via the PI3K/AKT Signal Pathway In Vivo and In Vitro.International journal of molecular sciences · 2025Article
- Transcriptome Analysis Suggests PKD3 Regulates Proliferative Glucose Metabolism, Calcium Homeostasis and Microtubule Dynamics After MEF Spontaneous Immortalization.International journal of molecular sciences · 2025Article
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- Role of depression-mediated alterations in pro-inflammatory cytokines in carcinogenesis.Frontiers in immunology · 2025Review
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11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMesenchymal stem/stromal cells (MSCs) acquire immunosuppressive capacity only in an inflammatory microenvironment. This can be recapitulated in vitro by treating MSCs with inflammatory cytokines TNFα and IFNγ, which induce indoleamine 2,3-dioxygenase (IDO) and TNF-stimulated gene-6 (TSG-6). However, the signaling pathways downstream of the cytokines remain to be elucidated.
methodsInflammatory bowel disease (IBD) mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. Human UC-MSCs were pretreated with TNF-α and IFN-γ for 24 h and were then infused intravenously at day 2 of DSS administration. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay. Real-time PCR and Western blot were used to examine the mRNA level and protein expression. MSCs overexpressing constitutive active AKT or dominant negative AKT were generated and were analyzed. The glycolysis level of the MSCs was measured using Extracellular Flux Analyzer. 2-NBDG was used to monitor the uptake of glucose by MSCs.
resultsTNFα and IFNγ treatment led to rapid consumption of glucose and metabolic skewing toward glycolysis in MSCs, which was required for the therapeutic efficacy of MSCs on IBD. Blockade of glycolysis in MSCs inhibited the expression of immunomodulatory molecules, IDO and TSG-6, as well as the therapeutic effect on IBD. Moreover, PI3K-AKT signaling axis was rapidly activated and was required for the skewing toward glycolysis induced by TNFα and IFNγ. MSCs expressing dominant negative AKT were compromised in their therapeutic efficacy on IBD.
conclusionThe glycolysis-dependent anti-inflammatory property of MSCs conferred by inflammatory cytokines is mediated by PI3K-AKT signaling pathway.
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