ArticlePloS one2017
RIG-I and IL-6 are negative-feedback regulators of STING induced by double-stranded DNA.
Article in PloS one, 2017. 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, 31 citations in OpenAlex.
- Article
- Targeting the cGAS-STING pathway: emerging strategies and challenges for the treatment of inflammatory skin diseases.Frontiers in pharmacology · 2025Review
- (-)-α-Bisabolol inhibits D-Gal-induced HSF cellular senescenceIranian journal of basic medical sciences · 2024Article
- Article
- cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging.Frontiers in immunology · 2023Review
- Effect of stimulator of interferon genes (STING) signaling on radiation-induced chemokine expression in human osteosarcoma cells.PloS one · 2023Article
- Genomic Amplification ofCells · 2022Article
- Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers.Frontiers in immunology · 2022Article
- Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing.Experimental & molecular medicine · 2021Review
- cGAS-STING cytosolic DNA sensing pathway is suppressed by JAK2-STAT3 in tumor cells.Scientific reports · 2021Article
- The herpesvirus accessory protein γ134.5 facilitates viral replication by disabling mitochondrial translocation of RIG-I.PLoS pathogens · 2021Article
- S1P Generation by Sphingosine Kinase-2 in Recruited Macrophages Resolves Lung Inflammation by Blocking STING Signaling in Alveolar Macrophages.Journal of cellular signaling · 2021Article
- Pharmacological Targeting of STING-Dependent IL-6 Production in Cancer Cells.Frontiers in cell and developmental biology · 2021Article
- The role of the adaptor molecule STING during Schistosoma mansoni infection.Scientific reports · 2020Article
- Influenza PB1-F2 Inhibits Avian MAVS Signaling.Viruses · 2020Article
- Trust as a mediator in the relationship between childhood sexual abuse and IL-6 level in adulthood.PloS one · 2020Article
- Nanoparticle Delivery of RIG-I Agonist Enables Effective and Safe Adjuvant Therapy in Pancreatic Cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Post-translational Control of Innate Immune Signaling Pathways by Herpesviruses.Frontiers in microbiology · 2019Review
- Functional Characterization of Duck STING in IFN-β Induction and Anti-H9N2 Avian Influenza Viruses Infections.Frontiers in immunology · 2019Article
- miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1).Scientific reports · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stimulator of interferon genes (STING) protein has emerged as a critical signal transduction molecule in the innate immune response. Sustained activation of the STING signaling induced by cytosolic DNA has been considered to be the cause of a variety of autoimmune diseases characterized by uncontrolled inflammation. Therefore, it is important to understand the molecular basis of the regulation of STING signaling pathway. Here we demonstrate that the STING protein undergoes a proteasome-mediated degradation in human diploid cell (HDC) lines including MRC-5 following the transfection of double-stranded DNA (dsDNA). The degradation of STING is accompanied by the increased expression of both RIG-I and IL-6. Employing the RIG-I siRNA knockdown and an IL-6 neutralizing antibody greatly inhibits the degradation of STING induced by dsDNA. We further demonstrate that both IL-6 and RIG-I are downstream molecules of STING along the DNA sensor pathway. Therefore, STING degradation mediated by RIG-I and IL-6 may serve as a negative feedback mechanism to limit the uncontrolled innate immune response induced by dsDNA. We have further shown that RIG-I and IL-6 promote STING degradation by activating/dephosphorylating UNC-51-like kinase (ULK1). Interestingly, the STING protein is not significantly affected by dsDNA in non-HDC HEK293 cells. Our study thus has identified a novel signaling pathway for regulating STING in HDCs.
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Registered trials
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