ArticleJournal of neuroinflammation2015
Fingolimod induces neuroprotective factors in human astrocytes.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Meta-analysis of mouse transcriptomic studies supports a context-dependent astrocyte reaction in acute CNS injury versus neurodegeneration.Journal of neuroinflammation · 2020Pooled it
- The effect of fingolimod on focal and diffuse grey matter damage in active MS patients.Journal of neurology · 2018Trial
- Potential Role of Sphingosine-1-Phosphate and Its Receptors in the Reparative Processes of the Adult Brain.International journal of molecular sciences · 2026Review
- NPC1 deficiency engages a lysosome-genome-immune program linked to neurodegeneration and cellular aging signatures.bioRxiv : the preprint server for biology · 2026Article
- LncRNA AFAP1-AS1 mediates therapy-dependent expression of CCL5, CXCL10 and MMP9 in multiple sclerosis.Biochemistry and biophysics reports · 2026Article
- Association of Neurodevelopmental Disorders and Congenital Anomalies With Prenatal Multiple Sclerosis Treatment-Real-World Historical Cohort Study.Clinical pharmacology and therapeutics · 2026Article
- HBEGF/EGFR pathway activation by hUC-MSCs improves cognitive outcomes in anti-NMDAR encephalitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- How do different cell populations orchestrate myelin regeneration?Biochemical Society transactions · 2025Review
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- Neurotrophic factors in multiple sclerosis.Frontiers in immunology · 2025Review
- Disease-Modifying Symptomatic Treatment (DMST): The Potential Role of Vortioxetine in the Treatment of Depression in Patients with Multiple Sclerosis.Current neuropharmacology · 2025Review
- The astrocyte-produced growth factor HB-EGF limits autoimmune CNS pathology.Nature immunology · 2024Article
- Research progress of autoimmune diseases based on induced pluripotent stem cells.Frontiers in immunology · 2024Review
- Investigating the Mitoprotective Effects of S1P Receptor Modulators Ex Vivo Using a Novel Semi-Automated Live Imaging Set-Up.International journal of molecular sciences · 2023Article
- Article
- Repurposing drugs against Alzheimer's disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD?Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
- Cure of Alzheimer's Dementia Requires Addressing All of the Affected Brain Cell Types.Journal of clinical medicine · 2023Article
- Supplementary Pharmacotherapy for the Behavioral Abnormalities Caused by Stressors in Humans, Focused on Post-Traumatic Stress Disorder (PTSD).Journal of clinical medicine · 2023Article
- Formulating treatment of major psychiatric disorders: algorithm targets the dominantly affected brain cell-types.Discover mental health · 2023Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFingolimod (FTY720) is the first sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of multiple sclerosis. The phosphorylated active metabolite FTY720-phosphate (FTY-P) interferes with lymphocyte trafficking. In addition, it accumulates in the CNS and reduces brain atrophy in multiple sclerosis (MS), and neuroprotective effects are hypothesized.
methodsHuman primary astrocytes as well as human astrocytoma cells were stimulated with FTY-P or S1P. We analyzed gene expression by a genome-wide microarray and validated induced candidate genes by quantitative PCR (qPCR) and ELISA. To identify the S1P-receptor subtypes involved, we applied a membrane-impermeable S1P analog (dihydro-S1P), receptor subtype specific agonists and antagonists, as well as RNAi silencing.
resultsFTY-P induced leukemia inhibitory factor (LIF), interleukin 11 (IL11), and heparin-binding EGF-like growth factor (HBEGF) mRNA, as well as secretion of LIF and IL11 protein. In order to mimic an inflammatory milieu as observed in active MS lesions, we combined FTY-P application with tumor necrosis factor (TNF). In the presence of this key inflammatory cytokine, FTY-P synergistically induced LIF, HBEGF, and IL11 mRNA, as well as secretion of LIF and IL11 protein. TNF itself induced inflammatory, B-cell promoting, and antiviral factors (CXCL10, BAFF, MX1, and OAS2). Their induction was blocked by FTY-P. After continuous exposure of cells to FTY-P or S1P for up to 7 days, the extent of induction of neurotrophic factors and the suppression of TNF-induced inflammatory genes declined but was still detectable. The induction of neurotrophic factors was mediated via surface S1P receptors 1 (S1PR1) and 3 (S1PR3).
conclusionsWe identified effects of FTY-P on astrocytes, namely induction of neurotrophic mediators (LIF, HBEGF, and IL11) and inhibition of TNF-induced inflammatory genes (CXCL10, BAFF, MX1, and OAS2). This supports the view that a part of the effects of fingolimod may be mediated via astrocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.