ArticleCell communication and signaling : CCS2013
A systems biology approach to suppress TNF-induced proinflammatory gene expressions.
Article in Cell communication and signaling : CCS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
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- Identifying Key In Silico Knockout for Enhancement of Limonene Yield Through Dynamic Metabolic Modelling.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Obsessive-Compulsive Disorder, PANDAS, and Tourette Syndrome: Immuno-inflammatory Disorders.Advances in experimental medicine and biology · 2023Review
- Effects of yoga practice on physiological distress, fatigue and QOL in patients affected by breast cancer undergoing adjuvant radiotherapy.Technical innovations & patient support in radiation oncology · 2022Article
- Marked to Die-Cell Death Mechanisms for Keratinocyte Acantholysis in Pemphigus Diseases.Life (Basel, Switzerland) · 2022Review
- Systems Biology to Understand and Regulate Human Retroviral Proinflammatory Response.Frontiers in immunology · 2021Review
- Involvement of tumor necrosis factor alpha in steroid-associated osteonecrosis of the femoral head: friend or foe?Stem cell research & therapy · 2019Article
- Defining rules for cancer cell proliferation in TRAIL stimulation.NPJ systems biology and applications · 2019Article
- Tumor necrosis factor-α -308 polymorphism in North Indian rheumatoid arthritis patients and association with mRNA and serum TNF-α.Clinical rheumatology · 2017Article
- Ultrastructural characterization of tumor necrosis factor alpha receptor type 1 distribution in the hypothalamic paraventricular nucleus of the mouse.Neuroscience · 2017Article
- Microbial Degradation of Cellular Kinases Impairs Innate Immune Signaling and Paracrine TNFα Responses.Scientific reports · 2016Article
- TNF-α gene polymorphisms and expression.SpringerPlus · 2016Review
- Clinical Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies Approved to Treat Rheumatoid Arthritis.Clinical pharmacokinetics · 2015Review
- The opioid antagonist, β-funaltrexamine, inhibits NF-κB signaling and chemokine expression in human astrocytes and in mice.European journal of pharmacology · 2015Article
- Systems Biology Strategy Reveals PKCδ is Key for Sensitizing TRAIL-Resistant Human Fibrosarcoma.Frontiers in immunology · 2014Article
- Parameter-less approaches for interpreting dynamic cellular response.Journal of biological engineering · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor necrosis factor (TNF) is a widely studied cytokine (ligand) that induces proinflammatory signaling and regulates myriad cellular processes. In major illnesses, such as rheumatoid arthritis and certain cancers, the expression of TNF is elevated. Despite much progress in the field, the targeted regulation of TNF response for therapeutic benefits remains suboptimal. Here, to effectively regulate the proinflammatory response induced by TNF, a systems biology approach was adopted.
resultsWe developed a computational model to investigate the temporal activations of MAP kinase (p38), nuclear factor (NF)-κB, and the kinetics of 3 groups of genes, defined by early, intermediate and late phases, in murine embryonic fibroblast (MEF) and 3T3 cells. To identify a crucial target that suppresses, and not abolishes, proinflammatory genes, the model was tested in several in silico knock out (KO) conditions. Among the candidate molecules tested, in silico RIP1 KO effectively regulated all groups of proinflammatory genes (early, middle and late). To validate this result, we experimentally inhibited TNF signaling in MEF and 3T3 cells with RIP1 inhibitor, Necrostatin-1 (Nec-1), and investigated 10 genes (Il6, Nfkbia, Jun, Tnfaip3, Ccl7, Vcam1, Cxcl10, Mmp3, Mmp13, Enpp2) belonging to the 3 major groups of upregulated genes. As predicted by the model, all measured genes were significantly impaired.
conclusionsOur results demonstrate that Nec-1 modulates TNF-induced proinflammatory response, and may potentially be used as a therapeutic target for inflammatory diseases such as rheumatoid arthritis and osteoarthritis.
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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.