ArticleJournal of neuroinflammation2016
Fractalkine shedding is mediated by p38 and the ADAM10 protease under pro-inflammatory conditions in human astrocytes.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- Neuronal DJ-1 regulates microglial activation in Parkinson's disease.Neural regeneration research · 2026Article
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Monocolonization withMicrobiology spectrum · 2026Article
- The ADAM Family of Proteases: Structure, Substrates, and Roles in Liver Diseases.International journal of molecular sciences · 2026Review
- Article
- Glycosaminoglycan binding to soluble CX3CL1 impacts monocyte migrationFrontiers in immunology · 2026Article
- Mitochondrial microprotein MOCCI controls neuroinflammation by altering glial activation states.Frontiers in immunology · 2026Article
- Identification of serum proteins associated with response of triple-negative breast cancer to neoadjuvant chemotherapy: preliminary results from the INSTIGO trial.Clinical proteomics · 2025Article
- Estrogen receptor 1 activation suppresses microglia-derived Tnf-α signaling as a photoreceptor self-protection mechanism.Journal of neuroinflammation · 2025Article
- Article
- Targeting CX3CR1 Signaling Dynamics: A Critical Determinant in the Temporal Regulation of Post-Stroke Neurorepair.Brain sciences · 2025Review
- CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis.International journal of molecular sciences · 2024Review
- Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.Progress in retinal and eye research · 2023Review
- The Cytokine CX3CL1 and ADAMs/MMPs in Concerted Cross-Talk Influencing Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Fractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease.Neural plasticity · 2023Review
- Potential significance of CX3CR1 dynamics in stress resilience against neuronal disorders.Neural regeneration research · 2022Review
- The role of ADAM10 in astrocytes: Implications for Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
- Glial PAMPering and DAMPening of Adult Hippocampal Neurogenesis.Brain sciences · 2021Review
- Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure.Scientific reports · 2021Article
- Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia.Pharmacological reports : PR · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe fractalkine (CX3CR1) ligand is expressed in astrocytes and reported to be neuroprotective. When cleaved from the membrane, soluble fractalkine (sCX3CL1) activates the receptor CX3CR1. Although somewhat controversial, CX3CR1 is reported to be expressed in neurons and microglia. The membrane-bound form of CX3CL1 additionally acts as an adhesion molecule for microglia and infiltrating white blood cells. Much research has been done on the role of fractalkine in neuronal cells; however, little is known about the regulation of the CX3CL1 ligand in astrocytes.
methodsThe mechanisms involved in the up-regulation and cleavage of CX3CL1 from human astrocytes were investigated using immunocytochemistry, Q-PCR and ELISA. All statistical analysis was performed using GraphPad Prism 5.
resultsA combination of ADAM17 (TACE) and ADAM10 protease inhibitors was found to attenuate IL-1β-, TNF-α- and IFN-γ-induced sCX3CL1 levels in astrocytes. A specific ADAM10 (but not ADAM17) inhibitor also attenuated these effects, suggesting ADAM10 proteases induce release of sCX3CL1 from stimulated human astrocytes. A p38 MAPK inhibitor also attenuated the levels of sCX3CL1 upon treatment with IL-1β, TNF-α or IFN-γ. In addition, an IKKβ inhibitor significantly reduced the levels of sCX3CL1 induced by IL-1β or TNF-α in a concentration-dependent manner, suggesting a role for the NF-kB pathway.
conclusionsIn conclusion, this study shows that the release of soluble astrocytic fractalkine is regulated by ADAM10 proteases with p38 MAPK also playing a role in the fractalkine shedding event. These findings are important for understanding the role of CX3CL1 in healthy and stimulated astrocytes and may benefit our understanding of this pathway in neuro-inflammatory and neurodegenerative diseases.
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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.