ArticleJournal of neuroinflammation2019
Soluble epoxide hydrolase modulates immune responses in activated astrocytes involving regulation of STAT3 activity.
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- TPPU protects against seizures and seizure-associated comorbidities by inhibiting the Akt/mTOR signaling pathway in KA-induced convulsant mice.Frontiers in immunology · 2026Article
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- Precision Enzyme: Targeted Drug Discovery in Neurodegenerative Disorders.Protein and peptide letters · 2025Review
- Soluble epoxide hydrolase inhibition preserves alveolar bone in experimental periodontitis with estrogen deficiency.Frontiers in immunology · 2025Article
- Mice deficient in the phosphatase activity of sEH show decreased levels of the endocannabinoid 2-AG in the olfactory bulb and depressive-like behavior.FEBS letters · 2024Article
- Review
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- The effects of venlafaxine on depressive-like behaviors and gut microbiome in cuprizone-treated mice.Frontiers in psychiatry · 2024Article
- rTMS ameliorates depressive-like behaviors and regulates the gut microbiome and medium- and long-chain fatty acids in mice exposed to chronic unpredictable mild stress.CNS neuroscience & therapeutics · 2023Article
- Arachidonic acid metabolism in health and disease.MedComm · 2023Review
- Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration.Nature reviews. Neurology · 2023Review
- The critical role of KLF4 in regulating the activation of A1/A2 reactive astrocytes following ischemic stroke.Journal of neuroinflammation · 2023Article
- Inhibition of sEH via stabilizing the level of EETs alleviated Alzheimer's disease through GSK3β signaling pathway.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2021Article
- Abnormal phosphorylation of tau protein and neuroinflammation induced by laparotomy in an animal model of postoperative delirium.Experimental brain research · 2021Article
- Discovery of Soluble Epoxide Hydrolase Inhibitors from Chemical Synthesis and Natural Products.Journal of medicinal chemistry · 2021Review
- Dextromethorphan Dampens Neonatal Astrocyte Activation and Endoplasmic Reticulum Stress Induced by Prenatal Exposure to Buprenorphine.Behavioural neurology · 2021Article
- Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAstrocyte activation is a common pathological feature in many brain diseases with neuroinflammation, and revealing the underlying mechanisms might shed light on the regulatory processes of the diseases. Recently, soluble epoxide hydrolase (sEH) has been proposed to affect neuroinflammation in brain injuries. However, the roles of astrocytic sEH in brains with neurodegeneration remain unclear.
methodsThe expression of astrocytic sEH in the brains of APPswe/PSEN1dE9 (APP/PS1) mice developing Alzheimer's disease (AD)-like pathology was evaluated by confocal imaging. LPS-activated primary astrocytes with mRNA silencing or overexpression of sEH were used to investigate its regulatory roles in astrocyte activation and the induction of pro-inflammatory markers. Primary astrocytes isolated from a sEH knockout (sEH
resultsThe immunoreactivity of sEH was increased in activated astrocytes in parallel with the progression of AD in APP/PS1 mice. Our data from primary astrocyte cultures further demonstrate that the overexpression of sEH ameliorated, while the silencing of sEH mRNA enhanced, the lipopolysaccharides (LPS)-induced expression of pro-inflammatory markers, such as inducible nitric oxide, cyclooxygenase 2 (COX-2), and pro-inflammatory cytokines. These findings suggest that sEH negatively regulates astrocyte immune responses. Enhanced immune responses found in LPS-activated sEH
conclusionsOur results provide evidence, for the first time, showing that sEH negatively regulates astrocytic immune responses and GFAP expression, while the underlying mechanism at least partly involves the downregulation of STAT3 phosphorylation. The discovery of a novel function for sEH in the negative control of astrocytic immune responses involving STAT3 activation confers further insights into the regulatory machinery of astrocyte activation during the development of neurodegeneration.
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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.