ArticlePloS one2013
Activation of protein tyrosine phosphatase non-receptor type 2 by spermidine exerts anti-inflammatory effects in human THP-1 monocytes and in a mouse model of acute colitis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer's Disease: A Systematic Review.Molecules (Basel, Switzerland) · 2020Pooled it
- Article
- Evaluating antioxidant treatment approaches for eosinophilic chronic sinusitis.Frontiers in immunology · 2026Review
- A Spermidine Derivative Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting the MAPK4/AKT Signaling Pathway.Foods (Basel, Switzerland) · 2025Article
- Role of polyamines in intestinal mucosal barrier function.Seminars in immunopathology · 2025Review
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- Engineered spermidine-secretingFrontiers in neuroscience · 2025Article
- Origin and Function of Monocytes in Inflammatory Bowel Disease.Journal of inflammation research · 2024Review
- Mechanism of electro-acupuncture in alleviating intestinal injury in septic mice via polyamine-related M2-macrophage polarization.Frontiers in immunology · 2024Article
- Spermidine Ameliorates Colitis via Induction of Anti-Inflammatory Macrophages and Prevention of Intestinal Dysbiosis.Journal of Crohn's & colitis · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- The upregulation of peripheral blood polyamine metabolites spermidine and spermine in children with hand, foot, mouth disease is related to enterovirus 71 capsid protein VP1, but not VP4.Translational pediatrics · 2023Article
- Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection.PloS one · 2023Article
- How autophagy, a potential therapeutic target, regulates intestinal inflammation.Frontiers in immunology · 2023Review
- Protein tyrosine phosphatase non-receptor type 2 as the therapeutic target of atherosclerotic diseases: past, present and future.Frontiers in pharmacology · 2023Review
- Bioengineering ofMetabolites · 2022Article
- PTPN2 in the Immunity and Tumor Immunotherapy: A Concise Review.International journal of molecular sciences · 2022Review
- Polyamines in cancer: integrating organismal metabolism and antitumour immunity.Nature reviews. Cancer · 2022Review
- Research Progress and Potential Applications of Spermidine in Ocular Diseases.Pharmaceutics · 2022Review
- Small Molecule Signatures of Mice Lacking T-cell p38 Alternate Activation, a Model for Immunosuppression Conditions, after Total-Body Irradiation.Radiation research · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSpermidine is a dietary polyamine that is able to activate protein tyrosine phosphatase non-receptor type 2 (PTPN2). As PTPN2 is known to be a negative regulator of interferon-gamma (IFN-γ)-induced responses, and IFN-γ stimulation of immune cells is a critical process in the immunopathology of inflammatory bowel disease (IBD), we wished to explore the potential of spermidine for reducing pro-inflammatory effects in vitro and in vivo.
methodsHuman THP-1 monocytes were treated with IFN-γ and/or spermidine. Protein expression and phosphorylation were analyzed by Western blot, cytokine expression by quantitative-PCR, and cytokine secretion by ELISA. Colitis was induced in mice by dextran sodium sulfate (DSS) administration. Disease severity was assessed by recording body weight, colonoscopy and histology.
resultsSpermidine increased expression and activity of PTPN2 in THP-1 monocytes and reduced IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT) 1 and 3, as well as p38 mitogen-activated protein kinase (MAPK) in a PTPN2 dependent manner. Subsequently, IFN-γ-induced expression/secretion of intracellular cell adhesion molecule (ICAM)-1 mRNA, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 was reduced in spermidine-treated cells. The latter effects were absent in PTPN2-knockdown cells. In mice with DSS-induced colitis, spermidine treatment resulted in ameliorated weight loss and decreased mucosal damage indicating reduced disease severity.
conclusionsActivation of PTPN2 by spermidine ameliorates IFN-γ-induced inflammatory responses in THP-1 cells. Furthermore, spermidine treatment significantly reduces disease severity in mice with DSS-induced colitis; hence, spermidine supplementation and subsequent PTPN2 activation may be helpful in the treatment of chronic intestinal inflammation such as IBD.
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Registered trials
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