ArticleJournal of immunology (Baltimore, Md. : 1950)2014
The natural product phyllanthusmin C enhances IFN-γ production by human NK cells through upregulation of TLR-mediated NF-κB signaling.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- Antitumor and immunomodulatory activities of diphyllin and its derivatives.Bioorganic & medicinal chemistry · 2025Review
- The immunostimulatory activity ofFrontiers in pharmacology · 2025Article
- B7H6 Serves as a Negative Prognostic Marker and an Immune Modulator in Human Pancreatic Cancer.Frontiers in oncology · 2022Article
- Advances in plant-derived natural products for antitumor immunotherapy.Archives of pharmacal research · 2021Review
- Development of Broad-Spectrum Antiviral Agents-Inspiration from Immunomodulatory Natural Products.Viruses · 2021Review
- Dihydromyricetin ameliorates liver fibrosis via inhibition of hepatic stellate cells by inducing autophagy and natural killer cell-mediated killing effect.Nutrition & metabolism · 2021Article
- Screening for Active Compounds Targeting Human Natural Killer Cell Activation Identifying Daphnetin as an Enhancer for IFN-γ Production and Direct Cytotoxicity.Frontiers in immunology · 2021Article
- Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment.Cell stress · 2020Review
- Transition Metal-Mediated Annulation Approaches for Synthesis of Arylnaphthalene Lignan Lactones.Frontiers in chemistry · 2020Review
- TLR1/2 orchestrate human plasmacytoid predendritic cell response to gram+ bacteria.PLoS biology · 2019Article
- Potential Anticancer Agents Characterized from Selected Tropical Plants.Journal of natural products · 2019Review
- Crosstalks between mTORC1 and mTORC2 variagate cytokine signaling to control NK maturation and effector function.Nature communications · 2018Article
- IFN-γ Induces Gastric Cancer Cell Proliferation and Metastasis Through Upregulation of Integrin β3-Mediated NF-κB Signaling.Translational oncology · 2018Article
- A Synthetic Disaccharide Derivative of Diphyllin, TAARD, Activates Human Natural Killer Cells to Secrete Interferon-GammaFrontiers in immunology · 2018Article
- LNGFR targets the Wnt/β-catenin pathway and promotes the osteogenic differentiation in rat ectomesenchymal stem cells.Scientific reports · 2017Article
- Black Raspberries Enhance Natural Killer Cell Infiltration into the Colon and Suppress the Progression of Colorectal Cancer.Frontiers in immunology · 2017Article
- Application of ImmunoScore Model for the Differentiation between Active Tuberculosis and Latent Tuberculosis Infection as Well as Monitoring Anti-tuberculosis Therapy.Frontiers in cellular and infection microbiology · 2017Article
- Discovery of Anticancer Agents of Diverse Natural Origin.Anticancer research · 2016Review
- Sustained elevation of NF-κB activity sensitizes offspring of maternal inflammation to hypertension via impairing PGC-1α recovery.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Natural products are a major source for cancer drug development. NK cells are a critical component of innate immunity with the capacity to destroy cancer cells, cancer-initiating cells, and clear viral infections. However, few reports describe a natural product that stimulates NK cell IFN-γ production and unravel a mechanism of action. In this study, through screening, we found that a natural product, phyllanthusmin C (PL-C), alone enhanced IFN-γ production by human NK cells. PL-C also synergized with IL-12, even at the low cytokine concentration of 0.1 ng/ml, and stimulated IFN-γ production in both human CD56(bright) and CD56(dim) NK cell subsets. Mechanistically, TLR1 and/or TLR6 mediated PL-C's activation of the NF-κB p65 subunit that in turn bound to the proximal promoter of IFNG and subsequently resulted in increased IFN-γ production in NK cells. However, IL-12 and IL-15Rs and their related STAT signaling pathways were not responsible for the enhanced IFN-γ secretion by PL-C. PL-C induced little or no T cell IFN-γ production or NK cell cytotoxicity. Collectively, we identify a natural product with the capacity to selectively enhance human NK cell IFN-γ production. Given the role of IFN-γ in immune surveillance, additional studies to understand the role of this natural product in prevention of cancer or infection in select populations are warranted.
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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.