ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Mechanistic role of microRNA-146a in endotoxin-induced differential cross-regulation of TLR signaling.
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 109 papers.
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Who cites it
109 citing papers in PubMed, 204 citations in OpenAlex.
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- Non-coding RNAs: emerging biomarkers and therapeutic targets in cancer and inflammatory diseases.Frontiers in oncology · 2025Review
- Role of miRNA in Highly Pathogenic H5 Avian Influenza Virus Infection: An Emphasis on Cellular and Chicken Models.Viruses · 2024Review
- Metabolic Endotoxemia: From the Gut to Neurodegeneration.International journal of molecular sciences · 2024Review
- Association of endometriosis with Sjögren's syndrome: Genetic insights (Review).International journal of molecular medicine · 2024Review
- Alzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes.Frontiers in cellular and infection microbiology · 2024Review
- MiRNA-146a-A Key Player in Immunity and Diseases.International journal of molecular sciences · 2023Review
- Gene augmentation for autosomal dominant retinitis pigmentosa using rhodopsin genomic loci nanoparticles in the P23HGene therapy · 2023Article
- miRNAs as Modern Biomarkers in Asthma Therapy.International journal of molecular sciences · 2023Review
- MicroRNAs and Periodontal Disease: Helpful Therapeutic Targets?Advanced pharmaceutical bulletin · 2023Review
- MicroRNA-127 promotes anti-microbial ability in porcine alveolar macrophages via S1PR3/TLR signaling pathway.Journal of veterinary science · 2023Article
- Plasma microRNAs as non-invasive biomarkers in bovine endometritis caused by Gram-negative and Gram-positive bacteria.Veterinary research forum : an international quarterly journal · 2023Article
- Inhibition of miR-146a Expression and Regulation of Endotoxin Tolerance by Rhesus Theta-Defensin-1.Mediators of inflammation · 2023Article
- Exosomes from IL-1β-Primed Mesenchymal Stem Cells Inhibited IL-1β- and TNF-α-Mediated Inflammatory Responses in Osteoarthritic SW982 Cells.Tissue engineering and regenerative medicine · 2021Article
- Lipopolysaccharide-Induced Exosomal miR-146a Is Involved in Altered Expression of Alzheimer's Risk Genes Via Suppression of TLR4 Signaling.Journal of molecular neuroscience : MN · 2021Article
- MiR-146a Negatively Regulates Aspergillus fumigatus-Induced TNF-α and IL-6 Secretion in THP-1 Macrophages.Mycopathologia · 2021Article
- MicroRNA-146a limits tumorigenic inflammation in colorectal cancer.Nature communications · 2021Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human TLRs are critical sensors for microbial components leading to the production of proinflammatory cytokines that are controlled by various mechanisms. Monocytes pretreated with LPS exhibit a state of hyporesponsiveness, referred to as cross-tolerance, to both homologous and heterologous ligands, which play a broader role in innate immunity. To date, LPS-induced cross-tolerance has not been examined regarding microRNA expression kinetics. In this study, THP-1 monocytes treated with various inflammatory ligands showed a continuous amplification of microRNA (miR)-146a over 24 h that is inversely correlated to TNF-α production. In contrast, inhibition of miR-146a showed a reciprocal effect. Thus, the characteristic upregulation of miR-146a in LPS-exposed THP-1 monocytes was studied for cross-tolerance. Strikingly, in LPS-tolerized THP-1 monocytes, only miR-146a showed a continuous overexpression, suggesting its crucial role in cross-tolerance. Similarly, peptidoglycan-primed THP-1 cells showed homologous tolerance associated with miR-146a upregulation. Subsequently, interchangeable differential cross-regulation was observed among non-LPS ligands. TLR2 and TLR5 ligands showed both homologous and heterologous tolerance correlated to miR-146a overexpression. More importantly, inflammatory responses to TLR4, TLR2, and TLR5 ligands were reduced due to knockdown of miR-146a targets IL-1R-associated kinase 1 or TNFR-associated factor 6, suggesting the regulatory effect of miR-146a on these TLRs signaling. Transfection of miR-146a into THP-1 cells caused reduction of TNF-α production, mimicking LPS-induced cross-tolerance. Aside from individual ligands, a whole bacterial challenge in LPS-primed THP-1 monocytes was accompanied by less TNF-α production, which is conversely correlated to miR-146a expression. Our studies have thus demonstrated that miR-146a plays a crucial role for in vitro monocytic cell-based endotoxin-induced cross-tolerance.
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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.