ArticleBMC bioinformatics2013
Elucidating the crosstalk mechanism between IFN-gamma and IL-6 via mathematical modelling.
Article in BMC bioinformatics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Distinct Immunomodulatory Strategies Guide Mesenchymal Stromal/Stem Cell-Mediated Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PD-L1 and IFN-γ modulate Non-Small Cell Lung Cancer (NSCLC) cell plasticity associated to immune checkpoint inhibitor (ICI)-mediated hyperprogressive disease (HPD).Journal of translational medicine · 2025Article
- Immune and hematologicak responses to the third dose of an mRNA COVID-19 vaccine: a six-month longitudinal study.Frontiers in cellular and infection microbiology · 2025Article
- Altered CD39 and CD73 Expression in Rheumatoid Arthritis: Implications for Disease Activity and Treatment Response.Biomolecules · 2023Article
- Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages.Inflammation · 2023Article
- Systemic maternal inflammation promotes ASD via IL-6 and IFN-γ.Bioscience reports · 2022Review
- Multiscale modeling of collective cell migration elucidates the mechanism underlying tumor-stromal interactions in different spatiotemporal scales.Scientific reports · 2022Article
- The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma-Recent Findings and Review.Biomedicines · 2022Review
- Deciphering signal transduction networks in the liver by mechanistic mathematical modelling.The Biochemical journal · 2022Article
- Interferon-γ: teammate or opponent in the tumour microenvironment?Nature reviews. Immunology · 2022Review
- Identification of Interleukin1β as an Amplifier of Interferon alpha-induced Antiviral Responses.PLoS pathogens · 2020Article
- Article
- Inflammatory Mediators Across the Spectrum of Ankle-Brachial Index.Journal of atherosclerosis and thrombosis · 2019Article
- The competitive nature of signal transducer and activator of transcription complex formation drives phenotype switching of T cells.Immunology · 2018Article
- Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F and IL-22 in PBMCs from Rheumatoid Arthritis Patients.The open rheumatology journal · 2018Article
- The myocardin-related transcription factor MKL co-regulates the cellular levels of two profilin isoforms.The Journal of biological chemistry · 2017Article
- From the Cover: Interplay Between IFN-γ and IL-6 Impacts the Inflammatory Response and Expression of Interferon-Regulated Genes in Environmental-Induced Autoimmunity.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Mathematical Models for Immunology: Current State of the Art and Future Research Directions.Bulletin of mathematical biology · 2016Review
- Single nucleotide polymorphisms/haplotypes associated with multiple rubella-specific immune response outcomes post-MMR immunization in healthy children.Immunogenetics · 2015Article
- Therapeutic vaccination with 4-1BB co-stimulation eradicates mouse acute myeloid leukemia.OncoimmunologyArticle
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInterferon-gamma (IFN-gamma) and interleukin-6 (IL-6) are multifunctional cytokines that regulate immune responses, cell proliferation, and tumour development and progression, which frequently have functionally opposing roles. The cellular responses to both cytokines are activated via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. During the past 10 years, the crosstalk mechanism between the IFN-gamma and IL-6 pathways has been studied widely and several biological hypotheses have been proposed, but the kinetics and detailed crosstalk mechanism remain unclear.
resultsUsing established mathematical models and new experimental observations of the crosstalk between the IFN-gamma and IL-6 pathways, we constructed a new crosstalk model that considers three possible crosstalk levels: (1) the competition between STAT1 and STAT3 for common receptor docking sites; (2) the mutual negative regulation between SOCS1 and SOCS3; and (3) the negative regulatory effects of the formation of STAT1/3 heterodimers. A number of simulations were tested to explore the consequences of cross-regulation between the two pathways. The simulation results agreed well with the experimental data, thereby demonstrating the effectiveness and correctness of the model.
conclusionIn this study, we developed a crosstalk model of the IFN-gamma and IL-6 pathways to theoretically investigate their cross-regulation mechanism. The simulation experiments showed the importance of the three crosstalk levels between the two pathways. In particular, the unbalanced competition between STAT1 and STAT3 for IFNR and gp130 led to preferential activation of IFN-gamma and IL-6, while at the same time the formation of STAT1/3 heterodimers enhanced preferential signal transduction by sequestering a fraction of the activated STATs. The model provided a good explanation of the experimental observations and provided insights that may inform further research to facilitate a better understanding of the cross-regulation mechanism between the two pathways.
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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.