ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2022
Decreased Astrocytic CCL2 Accounts for BAF-312 Effect on PBMCs Transendothelial Migration Through a Blood Brain Barrier in Vitro Model.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Intracerebral Hemorrhage Induces Monocyte TNF Signaling in Patients That Is Suppressed by BAF312.Annals of clinical and translational neurology · 2026Article
- The NLRP3 Inflammasome in Neuropsychiatric Disorders: Molecular Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Intracerebral hemorrhage induces monocyte TNF signaling that is suppressed by Siponimod (BAF312): a single-cell transcriptomics study in patients.medRxiv : the preprint server for health sciences · 2026Article
- The Involvement of Glial Cells in Blood-Brain Barrier Damage in Neuroimmune Diseases.International journal of molecular sciences · 2024Review
- Increased NLRP3 Inflammasome Activation and Pyroptosis in Patients With Multiple Sclerosis With Fingolimod Treatment Failure.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Human BBB-on-a-chip reveals barrier disruption, endothelial inflammation, and T cell migration under neuroinflammatory conditions.Frontiers in molecular neuroscience · 2023Article
- The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination.Multiple sclerosis and related disorders · 2023Review
- Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis.International journal of molecular sciences · 2022Article
- Microglia Contributes to BAF-312 Effects on Blood-Brain Barrier Stability.Biomolecules · 2022Article
- Astrocytes and Inflammatory T Helper Cells: A Dangerous Liaison in Multiple Sclerosis.Frontiers in immunology · 2022Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disruption of the blood brain barrier (BBB) is a common event in several neurological diseases and in particular, in multiple sclerosis (MS), it contributes to the infiltration of the central nervous system by peripheral inflammatory cells. Sphingosine-1-phosphate (S1P) is a bioactive molecule with pleiotropic effects. Agonists of S1P receptors such as fingolimod and siponimod (BAF-312) are in clinical practice for MS and have been shown to preserve BBB function in inflammatory conditions. Using an in vitro BBB model of endothelial-astrocytes co-culture exposed to an inflammatory insult (tumor necrosis factor-α and interferon-γ; T&I), we show that BAF-312 reduced the migration of peripheral blood mononuclear cells (PBMCs) through the endothelial layer, only in the presence of astrocytes. This effect was accompanied by decreased expression of the adhesion molecule ICAM-1. BAF-312 also reduced the activation of astrocytes, by controlling NF-kB and NLRP3 induction and preventing the increase of proinflammatory cytokine and chemokines. Reduction of CCL2 by BAF-312 may be responsible for the observed effects and, accordingly, addition of exogenous CCL2 was able to counteract BAF-312 effects and rescued T&I responses on PBMC migration, ICAM-1 expression and astrocyte activation. The present results further point out BAF-312 effects on BBB properties, suggesting also the key role of astrocytes in mediating drug effects on endothelial function.
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