ArticleThe Journal of biological chemistry2016
Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual-specificity Phosphatase 1 (DUSP1): IMPLICATIONS FOR REGULATION BY GLUCOCORTICOIDS.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- Biogenesis of TNF-α-insights into proteostasis and inflammation.The FEBS journal · 2026Review
- The ZFP36 Family as Post-Transcriptional Regulators in Physiology and Disease.International journal of molecular sciences · 2026Review
- Global analysis of the abundance of AU-rich mRNAs in response to glucocorticoid treatment.Scientific reports · 2024Article
- Biophysically Interpretable Inference of Cell Types from Multimodal Sequencing Data.bioRxiv : the preprint server for biology · 2023Article
- Post-transcriptional checkpoints in autoimmunity.Nature reviews. Rheumatology · 2023Review
- FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis.The Kaohsiung journal of medical sciences · 2023Article
- Cellular and transcriptome signatures unveiled by single-cell RNA-Seq followingFrontiers in immunology · 2023Article
- Differential Effects of Toll-Like Receptor Activation and Differential Mediation by MAP Kinases of Immune Responses in Microglial Cells.Cellular and molecular neurobiology · 2022Article
- Single-Cell Transcriptome Profiling Signatures and Alterations of Microglia Associated With Glioblastoma Associate Microglia Contribution to Tumor Formation.Pathology oncology research : POR · 2022Article
- Interleukin-1β Induces Tissue Factor Expression in A549 Cells via EGFR-Dependent and -Independent Mechanisms.International journal of molecular sciences · 2021Article
- MicroRNA-423 Drug Resistance and Proliferation of Breast Cancer Cells by Targeting ZFP36.OncoTargets and therapy · 2020Article
- Network Topologies That Can Achieve Dual Function of Adaptation and Noise Attenuation.Cell systems · 2019Article
- The early detection of asthma based on blood gene expression.Molecular biology reports · 2019Article
- RNA-binding proteins control gene expression and cell fate in the immune system.Nature immunology · 2018Review
- Role and regulation of MKP-1 in airway inflammation.Respiratory research · 2017Review
- Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance.The Journal of biological chemistry · 2017Review
- Glucocorticoid receptors: finding the middle ground.The Journal of clinical investigation · 2017Review
- Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin.Scientific reports · 2017Article
- Long-acting βAmerican journal of physiology. Lung cellular and molecular physiology · 2017Article
- Understanding how long-acting βBritish journal of pharmacology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
TNF is central to inflammation and may play a role in the pathogenesis of asthma. The 3'-untranslated region of the TNF transcript contains AU-rich elements (AREs) that are targeted by the RNA-binding protein, tristetraprolin (also known as zinc finger protein 36 (ZFP36)), which is itself up-regulated by inflammatory stimuli, to promote mRNA degradation. Using primary human bronchial epithelial and pulmonary epithelial A549 cells, we confirm that interleukin-1β (IL1B) induces expression of dual-specificity phosphatase 1 (DUSP1), ZFP36, and TNF. Whereas IL1B-induced DUSP1 is involved in feedback control of MAPK pathways, ZFP36 exerts negative (incoherent) feed-forward control of TNF mRNA and protein expression. DUSP1 silencing increased IL1B-induced ZFP36 expression at 2 h and profoundly repressed TNF mRNA at 6 h. This was partly due to increased TNF mRNA degradation, an effect that was reduced by ZFP36 silencing. This confirms a regulatory network, whereby DUSP1-dependent negative feedback control reduces feed-forward control by ZFP36. Conversely, whereas DUSP1 overexpression and inhibition of MAPKs prevented IL1B-induced expression of ZFP36, this was associated with increased TNF mRNA expression at 6 h, an effect that was predominantly due to elevated transcription. This points to MAPK-dependent feed-forward control of TNF involving ZFP36-dependent and -independent mechanisms. In terms of repression by dexamethasone, neither silencing of DUSP1, silencing of ZFP36, nor silencing of both together prevented the repression of IL1B-induced TNF expression, thereby demonstrating the need for further repressive mechanisms by anti-inflammatory glucocorticoids. In summary, these data illustrate why understanding the competing effects of feedback and feed-forward control is relevant to the development of novel anti-inflammatory therapies.
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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.