ArticleThe EMBO journal2014
Specific calcineurin targeting in macrophages confers resistance to inflammation via MKP-1 and p38.
Article in The EMBO journal, 2014. 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, 32 citations in OpenAlex.
- Stromal cell-derived itaconate promotes endometriosis via macrophage NRF2 and lysosomal pH modulation.Redox biology · 2026Article
- Phosphatase-independent activity of smooth-muscle calcineurin orchestrates a gene expression program leading to hypertension.PLoS biology · 2025Article
- The regulatory role of immune microenvironment-related cells and pathways in the pathogenesis of keloids.Frontiers in immunology · 2025Review
- Targeting CaN/NFAT in Alzheimer's brain degeneration.Frontiers in immunology · 2023Review
- Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis.Frontiers in medicine · 2023Article
- The impact of belatacept on the phenotypic heterogeneity of renal T cell-mediated alloimmune response: The critical role of maintenance treatment and inflammatory load.Clinical transplantation · 2020Article
- Calcineurin-AKAP interactions: therapeutic targeting of a pleiotropic enzyme with a little help from its friends.The Journal of physiology · 2020Review
- Conditional deletion of Rcan1 predisposes to hypertension-mediated intramural hematoma and subsequent aneurysm and aortic rupture.Nature communications · 2018Article
- Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype.Nature communications · 2018Article
- Article
- Calcineurin inhibitors exacerbate coronary arteritis via the MyD88 signalling pathway in a murine model of Kawasaki disease.Clinical and experimental immunology · 2017Article
- Calcineurin-NFAT signalling in myeloid leucocytes: new prospects and pitfalls in immunosuppressive therapy.EMBO molecular medicine · 2017Review
- The Lymphatic System: Integral Roles in Immunity.Annual review of immunology · 2017Review
- Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome.Nature medicine · 2017Article
- Targeting the Monocyte-Macrophage Lineage in Solid Organ Transplantation.Frontiers in immunology · 2017Review
- Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death.American journal of respiratory and critical care medicine · 2016Article
- Crotamine stimulates phagocytic activity by inducing nitric oxide and TNF-α via p38 and NFκ-B signaling in RAW 264.7 macrophages.BMB reports · 2016Article
- C/EBPβ and Nuclear Factor of Activated T Cells Differentially Regulate Adamts-1 Induction by Stimuli Associated with Vascular Remodeling.Molecular and cellular biology · 2015Article
- Article
- Therapeutic strategies for anchored kinases and phosphatases: exploiting short linear motifs and intrinsic disorder.Frontiers in pharmacology · 2015Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages contribute to tissue homeostasis and influence inflammatory responses by modulating their phenotype in response to the local environment. Understanding the molecular mechanisms governing this plasticity would open new avenues for the treatment for inflammatory disorders. We show that deletion of calcineurin (CN) or its inhibition with LxVP peptide in macrophages induces an anti-inflammatory population that confers resistance to arthritis and contact hypersensitivity. Transfer of CN-targeted macrophages or direct injection of LxVP-encoding lentivirus has anti-inflammatory effects in these models. Specific CN targeting in macrophages induces p38 MAPK activity by downregulating MKP-1 expression. However, pharmacological CN inhibition with cyclosporin A (CsA) or FK506 did not reproduce these effects and failed to induce p38 activity. The CN-inhibitory peptide VIVIT also failed to reproduce the effects of LxVP. p38 inhibition prevented the anti-inflammatory phenotype of CN-targeted macrophages, and mice with defective p38-activation were resistant to the anti-inflammatory effect of LxVP. Our results identify a key role for CN and p38 in the modulation of macrophage phenotype and suggest an alternative treatment for inflammation based on redirecting macrophages toward an anti-inflammatory status.
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Registered trials
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.