ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Convergence of the mammalian target of rapamycin complex 1- and glycogen synthase kinase 3-β-signaling pathways regulates the innate inflammatory response.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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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.
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Who cites it
67 citing papers in PubMed, 103 citations in OpenAlex.
- Unlocking the gasotransmitter: hydrogen sulfide as a multitarget regulator in ischemia-reperfusion injury.Medical gas research · 2026Review
- Biphasic control of the B cell transcriptome by mTORC1 and GSK3.Cell reports · 2025Article
- Balancing Immunity: GSK-3's Divergent Roles in Dendritic Cell-Mediated T-Cell Priming and Memory Responses.International journal of molecular sciences · 2025Review
- Macrophages in the Context of Muscle Regeneration and Duchenne Muscular Dystrophy.International journal of molecular sciences · 2024Review
- Review
- α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect.Journal of neuroinflammation · 2023Review
- Emerging targets signaling for inflammation in Parkinson's disease drug discovery.Metabolic brain disease · 2022Review
- Sepsis-associated brain injury: underlying mechanisms and potential therapeutic strategies for acute and long-term cognitive impairments.Journal of neuroinflammation · 2022Review
- Successful combinatorial therapy of sirolimus and neuraminidase inhibitors in a patient with highly pathogenic avian influenza A (H5N6) virus: a case report.Annals of translational medicine · 2022Article
- Regulation of Autophagy by the Glycogen Synthase Kinase-3 (GSK-3) Signaling Pathway.International journal of molecular sciences · 2022Review
- mTOR Signaling Pathway Regulates the Release of Proinflammatory Molecule CCL5 Implicated in the Pathogenesis of Autism Spectrum Disorder.Frontiers in immunology · 2022Article
- Molecular Mechanisms of Muscle Fatigue.International journal of molecular sciences · 2021Review
- Glycogen Synthase Kinase-3: A Focal Point for Advancing Pathogenic Inflammation in Depression.Cells · 2021Review
- Article
- GSK-3α/β Activity Negatively Regulates MMP-1/9 Expression to SuppressFrontiers in immunology · 2021Article
- Genome-Wide Gene Expression Analysis of Mtb-Infected DC Highlights the Rapamycin-Driven Modulation of Regulatory CytokinesFrontiers in immunology · 2021Article
- Microglia mediated neuroinflammation - signaling regulation and therapeutic considerations with special reference to some natural compounds.Histology and histopathology · 2020Review
- Lithium chloride combination with rapamycin for the treatment of COVID-19 pneumonia.Medical hypotheses · 2020Article
- Glycogen Synthase Kinase-3β Mediates Proinflammatory Cytokine Secretion and Adipogenesis in Orbital Fibroblasts from Patients with Graves' Orbitopathy.Investigative ophthalmology & visual science · 2020Article
- Scutellarin Exerts Anti-Inflammatory Effects in Activated Microglia/Brain Macrophage in Cerebral Ischemia and in Activated BV-2 Microglia Through Regulation of MAPKs Signaling Pathway.Neuromolecular medicine · 2020Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The PI3K pathway and its regulation of mammalian target of rapamycin complex 1 (mTORC1) and glycogen synthase kinase 3 (GSK3) play pivotal roles in controlling inflammation. In this article, we show that mTORC1 and GSK3-β converge and that the capacity of mTORC1 to affect the inflammatory response is due to the inactivation of GSK3-β. Inhibition of mTORC1 attenuated GSK3 phosphorylation and increased its kinase activity. Immunoprecipitation and in vitro kinase assays demonstrated that GSK3-β associated with a downstream target of mTORC1, p85S6K, and phosphorylated GSK3-β. Inhibition of S6K1 abrogated the phosphorylation of GSK3-β while increasing and decreasing the levels of IL-12 and IL-10, respectively, in LPS-stimulated monocytes. In contrast, the direct inhibition of GSK3 attenuated the capacity of S6K1 inhibition to influence the levels of IL-10 and IL-12 produced by LPS-stimulated cells. At the transcriptional level, mTORC1 inhibition reduced the DNA binding of CREB and this effect was reversed by GSK3 inhibition. As a result, mTORC1 inhibition increased the levels of NF-κB p65 associated with CREB-binding protein. Inhibition of NF-κB p65 attenuated rapamycin's ability to influence the levels of pro- or anti-inflammatory cytokine production in monocytes stimulated with LPS. These studies identify the molecular mechanism by which mTORC1 affects GSK3 and show that mTORC1 inhibition regulates pro- and anti-inflammatory cytokine production via its capacity to inactivate GSK3.
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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.