ArticleMolecular immunology
Mammalian target of rapamycin (mTOR) regulates TLR3 induced cytokines in human oral keratinocytes.
Article in Molecular immunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- Immune Metabolism-An Opportunity to Better Understand Allergic Pathology and Improve Treatment of Allergic Diseases?Frontiers in allergy · 2022Article
- Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity.iScience · 2021Article
- Immunostimulant Bathing Influences the Expression of Immune- and Metabolic-Related Genes in Atlantic Salmon Alevins.Biology · 2021Article
- Cellular and physiological functions of C9ORF72 and implications for ALS/FTD.Journal of neurochemistry · 2021Review
- Mannan Oligosaccharides Application: Multipath Restriction FromFrontiers in immunology · 2021Article
- Article
- Cinnamaldehyde improves the growth performance and digestion and absorption capacity in grass carp (Ctenopharyngodon idella).Fish physiology and biochemistry · 2020Article
- MicroRNA-663 antagonizes apoptosis antagonizing transcription factor to induce apoptosis in epithelial cells.Apoptosis : an international journal on programmed cell death · 2019Article
- The IKK-related kinase TBK1 activates mTORC1 directly in response to growth factors and innate immune agonists.The EMBO journal · 2018Article
- Downregulation of c-Myc is involved in TLR3-mediated tumor death of neuroblastoma xenografts.Laboratory investigation; a journal of technical methods and pathology · 2016Article
- S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3.Nature immunology · 2016Article
- Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan.Frontiers in genetics · 2016Review
- The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation.Oncogene · 2015Article
- Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production.Nucleus (Austin, Tex.) · 2015Article
- Assessment of mTOR-Dependent Translational Regulation of Interferon Stimulated Genes.PloS one · 2015Article
- Article
- TLR2 promoter hypermethylation creates innate immune dysbiosis.Journal of dental research · 2015Article
- MicroRNA-26a negatively regulates toll-like receptor 3 expression of rat macrophages and ameliorates pristane induced arthritis in rats.Arthritis research & therapy · 2014Article
- Phosphoinositide-3 kinase inhibition modulates responses to rhinovirus by mechanisms that are predominantly independent of autophagy.PloS one · 2014Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies implicate the mammalian target of rapamycin (mTOR) pathway in the control of inflammatory responses following Toll-like receptor (TLR) stimulation in myeloid cells but its role in non-myeloid cells such as human keratinocytes is unknown. Here we show that TLR3 signaling can induce robust cytokine secretion including interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNFα), IL-12p70 and interferon beta (IFN-β), and our data reveal for the first time that inhibiting mTOR with rapamycin, suppresses these TLR3 induced responses but actually enhances bioactive IL-12p70 production in human oral keratinocytes. Rapamycin inhibited the phosphorylation of the 70-kDa ribosomal protein S6 kinase (p70S6K) and the 4E binding protein 1 (4EBP-1), and suppressed the mitogen activated protein kinase (MAPK) pathway by decreasing phosphorylation of c-Jun N-terminal kinase (JNK). We also show that TLR3 induces interferon regulatory factor 3 (IRF3) activation by Akt via an mTOR-p70S6K-4EBP1 pathway. Furthermore, we provide evidence that Poly I:C induced expression of IL-1β, TNFα, IL-12p70 and IFN-β was blocked by JNK inhibitor SP600125. TLR3 preferentially phosphorylated IKKα through mTOR to activate nuclear factor kappa beta (NF-κB) in human oral keratinocytes. Taken together, these data demonstrate p70S6K, p4EBP1, JNK, NF-κB and IRF3 are involved in the regulation of inflammatory mediators by TLR3 via the mTOR pathway. mTOR is a novel pathway modulating TLR3 induced inflammatory and antiviral responses in human oral keratinocytes.
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