ArticleNucleic acids research2017
TLR4-induced NF-κB and MAPK signaling regulate the IL-6 mRNA stabilizing protein Arid5a.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.
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- FIN56-induced ferroptosis suppresses the development of endometriosis by augmenting mitochondrial ROS and lipid peroxidation via the ACACA/ARID5A/NOX4 axis.Chinese medical journal · 2026Article
- TLR4-dependent upregulation of IL-22-producing T cells in the bone niche links to the imbalance of bone homeostasis.Cellular & molecular biology letters · 2026Article
- 3'-sialyllactose inhibits the migration and invasion of LPS-induced B16F10 mouse melanoma cells through inactivation of the NF-Glycoconjugate journal · 2026Article
- Dissecting temporal regulation of the TLR4-IL-6 axis using systematic targeted inhibition.Scientific reports · 2026Article
- Tooth Decay Promotes Senescence in Dental Pulp Stem Cells, Modifying Their Biological and Proteomic Profiles.Journal of cellular physiology · 2026Article
- Exploring promising biomarkers based on pathogenic mechanisms in interstitial cystitis/bladder pain syndrome.Nature reviews. Urology · 2026Review
- Immune-Enhancement Effects of 6-Methoxykaempferol on Cyclophosphamide-Induced Immunosuppression via Improving Antioxidant Enzyme Expression, NF-κB and MAPK Signaling, and Modulating Gut Microbiome.Antioxidants (Basel, Switzerland) · 2026Article
- N-Cadherin Dynamically Regulates Schwannoma Migration and Represents a Novel Therapeutic Target in NF2-Related Schwannomatosis.Research square · 2026Article
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- Immunomodulatory Effects of Lidocaine: Mechanisms of Actions and Therapeutic Applications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Multifunctional macrophage mimetic nanoplatform modulates vascular and epithelial double gut barriers to alleviate ulcerative colitis.Theranostics · 2026Article
- Bibliometric Analysis of Gut Microbiota and Hepatocellular Carcinoma: Research Trends and Frontiers.Journal of hepatocellular carcinoma · 2026Article
- Aflatoxin B1 Promotes M2-like Macrophage Polarization via IL-6 Expression in Hepatocellular Carcinoma.Digestive diseases and sciences · 2026Article
- Uridine Phosphorylase 1 as a Biomarker Associated with Glycolysis in Acute Lung Injury.Inflammation · 2025Article
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Lipid nanoparticles fromMolecular therapy. Methods & clinical development · 2025Article
- Cell-based evaluation of anti-inflammatory activity from the combination of natural compounds in LPS-stimulated U937 monocytes.Cytotechnology · 2025Article
46 more citing papers are in PubMed but not listed here.
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12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The AT-rich interactive domain-containing protein 5a (Arid5a) plays a critical role in autoimmunity by regulating the half-life of Interleukin-6 (IL-6) mRNA. However, the signaling pathways underlying Arid5a-mediated regulation of IL-6 mRNA stability are largely uncharacterized. Here, we found that during the early phase of lipopolysaccharide (LPS) stimulation, NF-κB and an NF-κB-triggered IL-6-positive feedback loop activate Arid5a gene expression, increasing IL-6 expression via stabilization of the IL-6 mRNA. Subsequently, mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) promotes translocation of AU-rich element RNA-binding protein 1 (AUF-1) from the nucleus to the cytoplasm, where it destabilizes Arid5a mRNA by binding to AU-rich elements in the 3΄ UTR. This results in downregulation of IL-6 mRNA expression. During the late phase of LPS stimulation, p38 MAPK phosphorylates Arid5a and recruits the WW domain containing E3 ubiquitin protein ligase 1 (WWP1) to its complex, which in turn ubiquitinates Arid5a in a K48-linked manner, leading to its degradation. Inhibition of Arid5a phosphorylation and degradation increases production of IL-6 mRNA. Thus, our data demonstrate that LPS-induced NF-κB and MAPK signaling are required to control the regulation of the IL-6 mRNA stabilizing molecule Arid5a. This study therefore substantially increases our understanding of the mechanisms by which IL-6 is regulated.
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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.