ArticlePloS one2012
A cell permeable peptide inhibitor of NFAT inhibits macrophage cytokine expression and ameliorates experimental colitis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- TRP120-dependent activation of noncanonical Wnt/NFAT signaling drives monocyte chemokine production inmSphere · 2026Article
- Redirecting microglia phenotype via inhibition of NFAT1 ameliorates deficits in mouse model of synucleinopathies.Experimental & molecular medicine · 2025Article
- Beyond the Toll-Like Receptor 4. Structure-Dependent Lipopolysaccharide Recognition Systems: How far are we?ChemMedChem · 2025Review
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- New opportunities to overcome T cell dysfunction: the role of transcription factors and how to target them.Trends in biochemical sciences · 2024Review
- Management of ulcerative colitis by dichloroacetate: Impact on NFATC1/NLRP3/IL1B signaling based on bioinformatics analysis combined with in vivo experimental verification.Inflammopharmacology · 2024Article
- Pharmacological strategies for mitigating anti-TNF biologic immunogenicity in rheumatoid arthritis patients.Current opinion in pharmacology · 2023Review
- Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis.Frontiers in medicine · 2023Article
- Article
- A novel lipidic peptide with potential to promote balanced effector-regulatory T cell responses.Scientific reports · 2022Article
- Metabolic preconditioning in CD4+ T cells restores inducible immune tolerance in lupus-prone mice.JCI insight · 2021Article
- Delivery of the VIVIT Peptide to Human Glioma Cells to Interfere with Calcineurin-NFAT Signaling.Molecules (Basel, Switzerland) · 2021Article
- Interferon-stimulated gene products as regulators of central carbon metabolism.The FEBS journal · 2021Article
- Isoform-Selective NFAT Inhibitor: Potential Usefulness and Development.International journal of molecular sciences · 2021Review
- Identification of Key Immune-Related Genes in the Progression of Septic Shock.Frontiers in genetics · 2021Article
- Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes.Frontiers in immunology · 2021Review
- A Peptidyl Inhibitor that Blocks Calcineurin-NFAT Interaction and Prevents Acute Lung Injury.Journal of medicinal chemistry · 2020Article
- The elevated serum levels of calcineurin and nuclear factor of activated T-cells 1 in children with Kawasaki disease.Pediatric rheumatology online journal · 2020Article
- Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes.Journal of leukocyte biology · 2020Article
- LncRNA NRON alleviates atrial fibrosis through suppression of M1 macrophages activated by atrial myocytes.Bioscience reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Nuclear factor of activated T cells (NFAT) plays a critical role in the development and function of immune and non-immune cells. Although NFAT is a central transcriptional regulator of T cell cytokines, its role in macrophage specific gene expression is less defined. Previous work from our group demonstrated that NFAT regulates Il12b gene expression in macrophages. Here, we further investigate NFAT function in murine macrophages and determined the effects of a cell permeable NFAT inhibitor peptide 11R-VIVIT on experimental colitis in mice. Treatment of bone marrow derived macrophages (BMDMs) with tacrolimus or 11R-VIVIT significantly inhibited LPS and LPS plus IFN-γ induced IL-12 p40 mRNA and protein expression. IL-12 p70 and IL-23 secretion were also decreased. NFAT nuclear translocation and binding to the IL-12 p40 promoter was reduced by NFAT inhibition. Experiments in BMDMs from IL-10 deficient (Il10(-/-)) mice demonstrate that inhibition of IL-12 expression by 11R-VIVIT was independent of IL-10 expression. To test its therapeutic potential, 11R-VIVIT was administered systemically to Il10(-/-) mice with piroxicam-induced colitis. 11R-VIVIT treated mice demonstrated significant improvement in colitis compared to mice treated with an inactive peptide. Moreover, decreased spontaneous secretion of IL-12 p40 and TNF in supernatants from colon explant cultures was demonstrated. In summary, NFAT, widely recognized for its role in T cell biology, also regulates important innate inflammatory pathways in macrophages. Selective blocking of NFAT via a cell permeable inhibitory peptide is a promising therapeutic strategy for the treatment of inflammatory bowel diseases.
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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.