ArticlePloS one2014
Interleukin-6 secretion by astrocytes is dynamically regulated by PI3K-mTOR-calcium signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting.Nature reviews. Immunology · 2026Review
- Regulatory mechanisms and research progress of astrocytes in the neuro-endocrine-immune network.Frontiers in human neuroscience · 2026Review
- Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.Children (Basel, Switzerland) · 2025Review
- Abnormal behaviors and glial responses in an animal model of tau pathology.Molecular brain · 2025Article
- Article
- Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancer.Current research in toxicology · 2024Article
- P2X4 signalling contributes to hyperactivity but not pain sensitization comorbidity in a mouse model of attention deficit/hyperactivity disorder.Frontiers in pharmacology · 2023Article
- Role of Pannexin-1-P2X7R signaling on cell death and pro-inflammatory mediator expression induced byFrontiers in immunology · 2022Article
- Metformin Treatment Attenuates Brain Inflammation and Rescues PACAP/VIP Neuropeptide Alterations in Mice Fed a High-Fat Diet.International journal of molecular sciences · 2021Article
- Aversive Learning Deficits and Depressive-Like Behaviors Are Accompanied by an Increase in Oxidative Stress in a Rat Model of Fetal Alcohol Spectrum Disorders: The Protective Effect of Rapamycin.International journal of molecular sciences · 2021Article
- S100B Inhibition Attenuates Intestinal Damage and Diarrhea Severity DuringFrontiers in cellular and infection microbiology · 2021Article
- Developing Biomarkers of Mild Traumatic Brain Injury: Promise and Progress of CNS-Derived Exosomes.Frontiers in neurology · 2021Review
- Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats.Molecular brain · 2020Article
- Astrocytic Calcium Dynamics Along the Pain Pathway.Frontiers in cellular neuroscience · 2020Review
- A study of sirolimus and mTOR kinase inhibitor in a hypomorphicAmerican journal of physiology. Renal physiology · 2019Article
- Effects of rapamycin and curcumin on inflammation and oxidative stress in vitro and in vivo - in search of potential anti-epileptogenic strategies for temporal lobe epilepsy.Journal of neuroinflammation · 2018Article
- Heme and hemoglobin suppress amyloid β-mediated inflammatory activation of mouse astrocytes.The Journal of biological chemistry · 2018Article
- Effect of hyaluronic acid hydrogels containing astrocyte-derived extracellular matrix and/or V2a interneurons on histologic outcomes following spinal cord injury.Biomaterials · 2018Article
- Using biomaterials to promote pro-regenerative glial phenotypes after nervous system injuries.Biomedical materials (Bristol, England) · 2018Review
- Rapamycin-Sensitive Late-LTP is Enhanced in the Hippocampus of IL-6 Transgenic Mice.Neuroscience · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
After contusion spinal cord injury (SCI), astrocytes become reactive and form a glial scar. While this reduces spreading of the damage by containing the area of injury, it inhibits regeneration. One strategy to improve the recovery after SCI is therefore to reduce the inhibitory effect of the scar, once the acute phase of the injury has passed. The pleiotropic cytokine interleukin-6 (IL-6) is secreted immediately after injury and regulates scar formation; however, little is known about the role of IL-6 in the sub-acute phases of SCI. Interestingly, IL-6 also promotes axon regeneration, and therefore its induction in reactive astrocytes may improve regeneration after SCI. We found that IL-6 is expressed by astrocytes and neurons one week post-injury and then declines. Using primary cultures of rat astrocytes we delineated the molecular mechanisms that regulate IL-6 expression and secretion. IL-6 expression requires activation of p38 and depends on NF-κB transcriptional activity. Activation of these pathways in astrocytes occurs when the PI3K-mTOR-AKT pathway is inhibited. Furthermore, we found that an increase in cytosolic calcium concentration was necessary for IL-6 secretion. To induce IL-6 secretion in astrocytes, we used torin2 and rapamycin to block the PI3K-mTOR pathway and increase cytosolic calcium, respectively. Treating injured animals with torin2 and rapamycin for two weeks, starting two weeks after injury when the scar has been formed, lead to a modest effect on mechanical hypersensitivity, limited to the period of treatment. These data, taken together, suggest that treatment with torin2 and rapamycin induces IL-6 secretion by astrocytes and may contribute to the reduction of mechanical hypersensitivity after SCI.
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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.