ArticleMolecular medicine (Cambridge, Mass.)1999
Zinc finger transcription factors as molecular targets for nitric oxide-mediated immunosuppression: inhibition of IL-2 gene expression in murine lymphocytes.
Article in Molecular medicine (Cambridge, Mass.), 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 75 citations in OpenAlex.
- S-nitrosylation of the zinc finger protein SRG1 regulates plant immunity.Nature communications · 2018Article
- S-nitrosoglutathione reductase-dependent PPARγ denitrosylation participates in MSC-derived adipogenesis and osteogenesis.The Journal of clinical investigation · 2015Article
- Nitric oxide and KLF4 protein epigenetically modify class II transactivator to repress major histocompatibility complex II expression during Mycobacterium bovis bacillus Calmette-Guerin infection.The Journal of biological chemistry · 2013Article
- Modulation of stretch-induced myocyte remodeling and gene expression by nitric oxide: a novel role for lipoma preferred partner in myofibrillogenesis.American journal of physiology. Heart and circulatory physiology · 2013Article
- S-nitrosylation in the regulation of gene transcription.Biochimica et biophysica acta · 2012Article
- Role of nitric oxide in developmental biology in plants, bacteria, and man.Current topics in pharmacology · 2011Article
- Transcriptional regulation of SP-B gene expression by nitric oxide in H441 lung epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2010Article
- Protein/DNA arrays identify nitric oxide-regulated cis-element and trans-factor activities some of which govern neuroblastoma cell viability.Nucleic acids research · 2007Article
- STAT5 proteins are involved in down-regulation of iron regulatory protein 1 gene expression by nitric oxide.The Biochemical journal · 2006Article
- Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements.Nucleic acids research · 2006Article
- Hierarchical change in antioxidant enzyme gene expression and activity in acute cardiac rejection: role of inducible nitric oxide synthase.Molecular and cellular biochemistry · 2005Article
- Nitric oxide and zinc homeostasis in acute lung injury.Proceedings of the American Thoracic Society · 2005Review
- Inhibition of bacterial DNA replication by zinc mobilization during nitrosative stress.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- An autocatalytic mechanism of protein nitrosylation.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNitric oxide (NO) has frequently been shown to display immunosuppressive activities. We describe here a molecular mechanism contributing to this effect. MATERIALS AND
methodsMurine T cell lymphoma EL4-6.1 cells were activated with the physiological stimulus interleukin (IL)-1beta to express IL-2 mRNA in the presence or absence of subtoxic concentrations of the physiological spontaneous NO donor S-nitrosocysteine (SNOC). Subsequently, semiquantitative RT-PCR and gel shift assays with nuclear extracts were performed to analyze the effects of NO on IL-2 mRNA expression and on the activity of the dominant regulating transcription factors Sp1, EGR-1, and NFATc.
resultsNO inhibits IL-1beta-induced IL-2 mRNA expression in EL4-6.1 cells. The suppressive activity of NO was concentration dependent and found to be completely reversible. Importantly, NO at the concentrations used induced neither apoptosis nor necrosis. Dominant regulation of IL-2 gene expression is known to reside in the zinc finger transcription factors Sp1 or EGR-1 and in the non-zinc finger protein NFAT. NO abrogates the DNA binding activities of recombinant Sp1 and EGR-1. More importantly, gel shift assays also showed a lack of DNA binding of native Sp1 derived from NO-treated nuclear extracts and that from NO-treated viable lymphocytes. This effect is selective, as the DNA binding activity of recombinant NFATc was not affected by NO.
conclusionInactivation of zinc finger transcription factors by NO appears to be a molecular mechanism in the immunosuppressive activity of NO in mammals, thus contributing to NO-mediated inhibition of IL-2 gene expression after physiological stimuli. The exact understanding of the molecular mechanism leading to NO-mediated, fully reversible suppression of immune reactions may lead to use of this naturally occurring tool as an aid in inflammatory diseases.
Indexed as
Identifiers
10656874PMC2230482W92508582What OpenQuestion holds
Registered trials
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