ArticleInnate immunity2009
Calcineurin inactivation leads to decreased responsiveness to LPS in macrophages and dendritic cells and protects against LPS-induced toxicity in vivo.
Article in Innate immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- A Reversibly Thermoresponsive, Theranostic Nanoemulgel for Tacrolimus Delivery to Activated Macrophages: Formulation and In Vitro Validation.Pharmaceutics · 2023Article
- Multiple Shades of Gray-Macrophages in Acute Allograft Rejection.International journal of molecular sciences · 2023Review
- The Role of the Oral Immune System in Oropharyngeal Candidiasis-Facilitated Invasion and Dissemination ofFrontiers in oral health · 2022Review
- Biomimetic sponges improve muscle structure and function following volumetric muscle loss.Journal of biomedical materials research. Part A · 2021Article
- Protein phosphatases in TLR signaling.Cell communication and signaling : CCS · 2021Review
- Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis.Journal of the American Society of Nephrology : JASN · 2020Article
- CpG-ODN-mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFκB inhibitory protein IκBβ to drive IL1α and IL1β expression.Immunology · 2020Article
- Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes.Journal of leukocyte biology · 2020Article
- From Crosstalk between Immune and Bone Cells to Bone Erosion in Infection.International journal of molecular sciences · 2019Review
- Calcineurin inhibitor Tacrolimus impairs host immune response against urinary tract infection.Scientific reports · 2019Article
- The Effect of Immunosuppressive Drugs on MDSCs in Transplantation.Journal of immunology research · 2018Review
- Revisiting the Concept of Targeting NFAT to Control T Cell Immunity and Autoimmune Diseases.Frontiers in immunology · 2018Review
- Calcineurin-NFAT signalling in myeloid leucocytes: new prospects and pitfalls in immunosuppressive therapy.EMBO molecular medicine · 2017Review
- Activated Microglia Desialylate and Phagocytose Cells via Neuraminidase, Galectin-3, and Mer Tyrosine Kinase.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Impairment of early fracture healing by skeletal muscle trauma is restored by FK506.BMC musculoskeletal disorders · 2017Article
- Nuclear factor of activated T cells regulates neutrophil recruitment, systemic inflammation, and T-cell dysfunction in abdominal sepsis.Infection and immunity · 2014Article
- Specific calcineurin targeting in macrophages confers resistance to inflammation via MKP-1 and p38.The EMBO journal · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Microbial components such as lipopolysaccharide (LPS) bind to Toll-like receptors (TLRs) and activate innate and inflammatory responses. Responses to LPS and other microbial components are limited by the activation of negative feedback mechanisms that reduce responsiveness to subsequent LPS exposure, often termed LPS tolerance. Our laboratory has previously shown that calcineurin, a phosphatase known for its activation of T cells via NFAT, negatively regulates the TLR pathway in macrophages; consequently, calcineurin inhibitors (FK506 and cyclosporin A) mimic TLR ligands in activating the TLR pathway, NF-KB, and associated innate and inflammatory responses. This study investigated the physiological consequences of calcineurin inactivation for LPS-induced inflammatory responses in vitro and in vivo using two models: calcineurin inhibition by FK506 (tacrolimus) and myeloid cell-specific calcineurin deletion. Activation of dendritic cells and macrophages with FK506 in vitro was shown to induce a state of reduced responsiveness to LPS (i.e. a form of LPS tolerance). Similarly, macrophages from FK506-treated mice or from mice in which the calcineurin B1 (CnB1) subunit was conditionally knocked out in myeloid cells were found to have diminished LPS-induced inflammatory responses. In addition, mice with CnB1-deficient myeloid cells and mice undergoing FK506 treatment showed improved survival and recovery when challenged with high doses of systemic LPS compared to controls. These results demonstrate that inactivation of calcineurin in macrophages and other myeloid cells by inhibition or deletion can induce a form of LPS tolerance and protect the host from LPS toxicity in vivo.
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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.