ArticleThe Journal of biological chemistry2008
Interleukin (IL) 1beta induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/IkappaB kinase alpha pathway targeting activator protein-1.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 1 of them a synthesis that pooled it.
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Who cites it
160 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Epigenome-wide association study of circulating interleukin-6 connects DNA methylation to immunometabolic and inflammatory health.Communications biology · 2026Pooled it
- Trial
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- Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis.Science advances · 2026Article
- Role of Interleukin-6 in Atherothrombosis and Myocardial Infarction.Current atherosclerosis reports · 2026Review
- Immune-Modulatory Mechanism of Compound Yeast Culture in the Liver of Weaned Lambs.Animals : an open access journal from MDPI · 2025Article
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- Comparative Examination of Feline Coronavirus and Canine Coronavirus Effects on Extracellular Vesicles Acquired from A-72 Canine Fibrosarcoma Cell Line.Veterinary sciences · 2025Article
- Enzyme-Based Anti-Inflammatory Therapeutics for Inflammatory Diseases.Pharmaceutics · 2025Review
- Inflammatory biomarkers for predicting postoperative atrial fibrillation in cardiac surgery.Journal of medicine and life · 2025Article
- IL-1R1 Blockade Boosts CD40 Agonist Immune Responses but Fails to Improve Efficacy or Reduce Hepatotoxicity in Pancreatic Cancer.bioRxiv : the preprint server for biology · 2025Article
- Roles of cytokines in modulatingFrontiers in parasitology · 2025Article
- AMIGO2 characterizes cancer-associated fibroblasts in metastatic colon cancer and induces the release of paracrine active tumorigenic secretomes.The Journal of pathology · 2025Article
- Targeting interleukin-1 signaling for renoprotection.Frontiers in immunology · 2025Review
- Maltol, a compound in Korean Red Ginseng, attenuates theJournal of ginseng research · 2024Article
100 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
Abstract
Here we describe a novel role for the phosphatidylinositol 3-kinase/AKT pathway in mediating induction of interleukin-6 (IL-6) in response to IL-1. Pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) inhibited IL-6 mRNA and protein production. Overexpression of either dominant-negative AKT or IkappaB kinase alpha mutant, IKKalphaT23A, containing a mutation in a functional AKT phosphorylation site, shown previously to be important for NFkappaB activation, completely abrogated IL-6 promoter activation in response to IL-1. However, mutation of the consensus NFkappaB site on the IL-6 promoter did not abrogate promoter activation by IL-1 in contrast to the AP-1 site mutation. IL-1 induces phosphorylation of IKKalpha on the NFkappaB inducing kinase (NIK) phosphorylation sites Ser(176)/Ser(180) and on the Thr(23) site, and although phosphorylation of IKKalphaT23 is inhibited both by LY294002 and wortmannin, phosphorylation of Ser(176)/Ser(180) is not. Neither inhibition of PI 3-kinase/AKT nor IKKalphaT23A overexpression affected IkappaBalpha degradation in response to IL-1. Only partial inhibition by dominant-negative AKT and no inhibitory effect of IKKalphaT23A was observed on an IL-6 promoter-specific NFkappaB site in contrast to significant inhibitory effects on the AP-1 site. Taken together, we have discovered a novel PI 3-kinase/AKT-dependent pathway in response to IL-1, encompassing PI 3-kinase/AKT/IKKalphaT23 upstream of AP-1. This novel pathway is a parallel pathway to the PI 3-kinase/AKT upstream of NFkappaB and both are involved in IL-6 gene transcription in response to IL-1.
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