ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Toll-like receptor-mediated production of IL-1Ra is negatively regulated by GSK3 via the MAPK ERK1/2.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Senescent Factors Suppress Innate Antiviral Immunity in Aged Mice via Two Distinct Mechanisms.Aging cell · 2026Article
- SHP2 inhibition and adjuvant therapy synergistically target KIT-mutant GISTs via ERK1/2-regulated GSK3β/cyclin D1 pathway.Clinical and translational medicine · 2025Article
- NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation.Zoological research · 2024Article
- A Protective Role of Canonical Wnt/Mediators of inflammation · 2024Review
- Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion.Marine drugs · 2023Article
- Shenfu injection attenuates cardiac dysfunction and inhibits apoptosis in septic mice.Annals of translational medicine · 2022Article
- Differential Cytokine Signatures of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Influenza Infection Highlight Key Differences in Pathobiology.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Glycogen Synthase Kinase-3: A Focal Point for Advancing Pathogenic Inflammation in Depression.Cells · 2021Review
- Modulation of LPS-induced inflammatory cytokine production by a novel glycogen synthase kinase-3 inhibitor.European journal of pharmacology · 2020Article
- Review
- Activation of Toll-Like Receptor 3 Induces Interleukin-1 Receptor Antagonist Expression by Activating the Interferon Regulatory Factor 3.Journal of innate immunity · 2020Article
- GSK3β inhibition attenuates LPS-induced IL-6 expression in porcine adipocytes.Scientific reports · 2018Article
- TNFα disrupts blood brain barrier integrity to maintain prolonged depressive-like behavior in mice.Brain, behavior, and immunity · 2018Article
- Phosphodiesterase 4B negatively regulates endotoxin-activated interleukin-1 receptor antagonist responses in macrophages.Scientific reports · 2017Article
- Glycogen synthase kinase 3β in Toll-like receptor signaling.BMB reports · 2016Review
- Lithium chloride antileukemic activity in acute promyelocytic leukemia is GSK-3 and MEK/ERK dependent.Leukemia · 2015Article
- Phagocytosed Clofazimine Biocrystals Can Modulate Innate Immune Signaling by Inhibiting TNFα and Boosting IL-1RA Secretion.Molecular pharmaceutics · 2015Article
- Cytokine-induced monocyte MMP-1 is negatively regulated by GSK-3 through a p38 MAPK-mediated decrease in ERK1/2 MAPK activation.Journal of leukocyte biology · 2015Article
- Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter.European journal of immunology · 2015Article
- Glycogen synthase kinase 3β ubiquitination by TRAF6 regulates TLR3-mediated pro-inflammatory cytokine production.Nature communications · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1beta, has been shown to regulate the progression of a variety of inflammatory diseases. Although experimental studies and clinical trials have demonstrated the importance of IL-1Ra in chronic inflammatory diseases, the cellular mechanisms responsible for regulating the endogenous production of IL-1Ra by innate immune cells are currently unresolved. In the present study, we identify that glycogen-synthase kinase 3 (GSK3) regulates the production of the anti-inflammatory cytokine IL-1Ra via its ability to regulate the MAPK ERK1/2 in TLR-stimulated cells. Elucidation of the cell-signaling pathway by which GSK3 controlled ERK activity demonstrated that GSK3 inhibition resulted in an abrogation in the levels of the inhibitory residue serine 71 on Rac1 and increased the ability of Rac1 to interact with and activate p21-activated protein kinase. siRNA-mediated knockdown of Rac1 attenuated the ability of GSK3 inhibition to augment phospho-ERK1/2 levels in LPS-stimulated immune cells. Moreover, inhibiting the ability of GSK3 to augment ERK1/2 activity abrogated enhanced IL-1Ra production by GSK3-inhibited cells. Our findings identify that GSK3 negatively regulates the levels of IL-1Ra produced by LPS-stimulated innate immune cells.
Indexed as
Identifiers
What OpenQuestion holds
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.