ArticleProceedings of the National Academy of Sciences of the United States of America1999
Calcineurin and vacuolar-type H+-ATPase modulate macrophage effector functions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 76 citations in OpenAlex.
- Unlocking the therapeutic potential of the NFAT pathway in kidney diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- TM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction.Nature communications · 2024Article
- Central carbon flux controls growth/damage balance for Streptococcus pyogenes.PLoS pathogens · 2023Article
- Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders.Cells · 2022Review
- Protein phosphatases in TLR signaling.Cell communication and signaling : CCS · 2021Review
- (Pro)renin Receptor Inhibition Reduces Plasma Cholesterol and Triglycerides but Does Not Attenuate Atherosclerosis in Atherosclerotic Mice.Frontiers in cardiovascular medicine · 2021Article
- Proteomic identification of a marker signature for MAPKi resistance in melanoma.The EMBO journal · 2019Article
- A novel autophagy enhancer as a therapeutic agent against metabolic syndrome and diabetes.Nature communications · 2018Article
- Proteomics-based insights into mitogen-activated protein kinase inhibitor resistance of cerebral melanoma metastases.Clinical proteomics · 2018Article
- Calcineurin inhibitors exacerbate coronary arteritis via the MyD88 signalling pathway in a murine model of Kawasaki disease.Clinical and experimental immunology · 2017Article
- Epiregulin (EREG) and human V-ATPase (TCIRG1): genetic variation, ethnicity and pulmonary tuberculosis susceptibility in Guinea-Bissau and The Gambia.Genes and immunity · 2014Article
- Comparative genomics RNAi screen identifies Eftud2 as a novel regulator of innate immunity.Genetics · 2014Article
- A cell permeable peptide inhibitor of NFAT inhibits macrophage cytokine expression and ameliorates experimental colitis.PloS one · 2012Article
- Understanding the role of host hemocytes in a squid/vibrio symbiosis using transcriptomics and proteomics.Frontiers in immunology · 2012Article
- Nuclear presence of nuclear factor of activated T cells (NFAT) c3 and c4 is required for Toll-like receptor-activated innate inflammatory response of monocytes/macrophages.Cellular signalling · 2011Article
- Proteomic biosignatures for monocyte-macrophage differentiation.Cellular immunology · 2011Article
- Human V-ATPase gene can protect or predispose the host to pulmonary tuberculosis.Genes and immunity · 2009Article
- HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits.Nature immunology · 2009Article
- NFATc1 mediates Toll-like receptor-independent innate immune responses during Trypanosoma cruzi infection.PLoS pathogens · 2009Article
- Calcineurin inactivation leads to decreased responsiveness to LPS in macrophages and dendritic cells and protects against LPS-induced toxicity in vivo.Innate immunity · 2009Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
While effector molecules produced by activated macrophages (including nitric oxide, tumor necrosis factor alpha, interleukin 1, etc.) help to eliminate pathogens, high levels of these molecules can be deleterious to the host itself. Despite their importance, the mechanisms modulating macrophage effector functions are poorly understood. This work introduces two key negative regulators that control the levels and duration of macrophage cytokine production. Vacuolar-type H+-ATPase (V-ATPase) and calcineurin (Cn) constitutively act in normal macrophages to suppress expression of inflammatory cytokines in the absence of specific activation and to inhibit macrophage cytokine responses induced by bacterial lipopolysaccharide (V-ATPase), interferon gamma (V-ATPase and Cn), and calcium (Ca2+) flux (Cn). Cn and V-ATPase modulate effector gene expression at the mRNA level by inhibiting transcription factor NF-kappaB. This negative regulation by Cn is opposite to its crucial positive role in T cells, where it activates NFAT transcription factor(s) leading to expression of interleukin 2, tumor necrosis factor alpha, and other cytokine genes. The negative effects of V-ATPase and Cn on NF-kappaB-dependent gene expression are not limited to the macrophage lineage, as similar effects have been seen with a murine fibroblast cell line and with primary astrocytes.
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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.