ArticleThe Journal of biological chemistry2015
Pellino-1 Positively Regulates Toll-like Receptor (TLR) 2 and TLR4 Signaling and Is Suppressed upon Induction of Endotoxin Tolerance.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Pellino1-mTOR/S6K1 signaling axis is a key pathogenesis for the development of polycystic kidney disease.Cell death & disease · 2026Article
- Regulation of Neuroinflammation by Microglial DUBA-IRAK1-IKKβ Signaling Loop.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Anti-inflammatory mechanism of total flavonoids fromFrontiers in immunology · 2025Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Pellino 3 promotes the colitis-associated colorectal cancer through suppression of IRF4-mediated negative regulation of TLR4 signalling.Molecular oncology · 2023Article
- Induction of Antimicrobial Protein S100A15 Expression by Oral Microbial Pathogens Is Toll-like Receptors-Dependent Activation of c-Jun-N-Terminal Kinase (JNK), p38, and NF-κB Pathways.International journal of molecular sciences · 2023Article
- The roles of E3 ubiquitin ligases in cancer progression and targeted therapy.Clinical and translational medicine · 2023Review
- Biology of Pellino1: a potential therapeutic target for inflammation in diseases and cancers.Frontiers in immunology · 2023Review
- The Emerging Roles of Pellino Family in Pattern Recognition Receptor Signaling.Frontiers in immunology · 2022Review
- Herbal melanin induces interleukin-1β secretion and production by human THP-1 monocytes via Toll-like receptor 2 and p38 MAPK activation.Experimental and therapeutic medicine · 2021Article
- Ubiquitination as an Important Host-Immune Response Strategy in Penaeid Shrimp: Inferences From Other Species.Frontiers in immunology · 2021Review
- Ubiquitination of interleukin-1α is associated with increased pro-inflammatory polarization of murine macrophages deficient in the E3 ligase ITCH.The Journal of biological chemistry · 2020Article
- Treatment with the antipsychotic risperidone is associated with increased M1-like JAK-STAT1 signature gene expression in PBMCs from participants with psychosis and THP-1 monocytes and macrophages.International immunopharmacology · 2020Article
- Negative Effects of SIGIRR on TRAF6 Ubiquitination in Acute Lung Injury In Vitro.Journal of immunology research · 2020Article
- Pellino-1 Regulates the Responses of the Airway to Viral Infection.Frontiers in cellular and infection microbiology · 2020Article
- Unexpected Activities in Regulating Ciliation Contribute to Off-target Effects of Targeted Drugs.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Pellino-1 Regulates Immune Responses toFrontiers in immunology · 2019Article
- Increased A20-E3 ubiquitin ligase interactions in bid-deficient glia attenuate TLR3- and TLR4-induced inflammation.Journal of neuroinflammation · 2018Article
- DeSUMOylation of MKK7 kinase by the SUMO2/3 protease SENP3 potentiates lipopolysaccharide-induced inflammatory signaling in macrophages.The Journal of biological chemistry · 2018Article
- Beauvericin, a cyclic peptide, inhibits inflammatory responses in macrophages by inhibiting the NF-κB pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Endotoxin tolerance reprograms Toll-like receptor (TLR) 4-mediated macrophage responses by attenuating induction of proinflammatory cytokines while retaining expression of anti-inflammatory and antimicrobial mediators. We previously demonstrated deficient TLR4-induced activation of IL-1 receptor-associated kinase (IRAK) 4, IRAK1, and TANK-binding kinase (TBK) 1 as critical hallmarks of endotoxin tolerance, but mechanisms remain unclear. In this study, we examined the role of the E3 ubiquitin ligase Pellino-1 in endotoxin tolerance and TLR signaling. LPS stimulation increased Pellino-1 mRNA and protein expression in macrophages from mice injected with saline and in medium-pretreated human monocytes, THP-1, and MonoMac-6 cells, whereas endotoxin tolerization abrogated LPS inducibility of Pellino-1. Overexpression of Pellino-1 in 293/TLR2 and 293/TLR4/MD2 cells enhanced TLR2- and TLR4-induced nuclear factor κB (NF-κB) and expression of IL-8 mRNA, whereas Pellino-1 knockdown reduced these responses. Pellino-1 ablation in THP-1 cells impaired induction of myeloid differentiation primary response protein (MyD88), and Toll-IL-1R domain-containing adapter inducing IFN-β (TRIF)-dependent cytokine genes in response to TLR4 and TLR2 agonists and heat-killed Escherichia coli and Staphylococcus aureus, whereas only weakly affecting phagocytosis of heat-killed bacteria. Co-expressed Pellino-1 potentiated NF-κB activation driven by transfected MyD88, TRIF, IRAK1, TBK1, TGF-β-activated kinase (TAK) 1, and TNFR-associated factor 6, whereas not affecting p65-induced responses. Mechanistically, Pellino-1 increased LPS-driven K63-linked polyubiquitination of IRAK1, TBK1, TAK1, and phosphorylation of TBK1 and IFN regulatory factor 3. These results reveal a novel mechanism by which endotoxin tolerance re-programs TLR4 signaling via suppression of Pellino-1, a positive regulator of MyD88- and TRIF-dependent signaling that promotes K63-linked polyubiquitination of IRAK1, TBK1, and TAK1.
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