Microglial Phenotype Is Regulated by Activity of the Transcription Factor, NFAT (Nuclear Factor of Activated T Cells)
- 14 July 2010
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 30 (28), 9641-9646
- https://doi.org/10.1523/jneurosci.0828-10.2010
Abstract
The transcription factor family, nuclear factor of activated T cells (NFAT), regulates immune cell phenotype. Four different calcium/calmodulin-regulated isoforms have been identified in the periphery, but isoform expression in microglia, the resident immune cells of the CNS, has not been fully defined. In this study microglial NFAT isoform expression and involvement in regulating inflammatory responses in murine primary microglia culture was examined. Western blot analysis demonstrated robust detection of NFATc1 and c2 isoforms in microglia. Electrophoretic mobility shift assays demonstrated increased NFAT-DNA binding from nuclear extracts of lipopolysaccharide (LPS) stimulated microglia. Moreover, LPS-stimulated microglia behaved similarly to T cell receptor agonist antibody-stimulated Jurkat cells demonstrating a transient increase in NFAT-driven luciferase reporter gene expression. LPS-induced NFAT-luciferase activity in microglia was attenuated by pretreatment with tat-VIVIT, a cell-permeable NFAT inhibitory peptide. Furthermore, LPS-mediated secretion of microglial cytokines, TNF-α and MCP-1, was decreased by treatment with tat-VIVIT but not with tat-VEET, a negative control peptide. These results demonstrate that NFAT plays a role in regulating proinflammatory responses in cultured murine microglia.This publication has 41 references indexed in Scilit:
- Nuclear Factor of Activated T-Cells Isoform c4 (NFATc4/NFAT3) as a Mediator of Antiapoptotic Transcription in NMDA Receptor-Stimulated Cortical NeuronsJournal of Neuroscience, 2009
- Cognitive Decline in Alzheimer's Disease Is Associated with Selective Changes in Calcineurin/NFAT SignalingJournal of Neuroscience, 2009
- Evidence for Coregulation of Myocardial Gene Expression by MEF2 and NFAT in Human Heart FailureCirculation: Cardiovascular Genetics, 2009
- Beta amyloid oligomers and fibrils stimulate differential activation of primary microgliaJournal of Neuroinflammation, 2009
- Alternative splicing and expression of human and mouse NFAT genesGenomics, 2008
- TAT-Mediated Protein Transduction of Nogo Extracellular Peptide 1-40 and its Biological ActivityCellular and Molecular Neurobiology, 2008
- Interleukin-1β-dependent Signaling between Astrocytes and Neurons Depends Critically on Astrocytic Calcineurin/NFAT ActivityPublished by Elsevier BV ,2008
- NFAT and NFκB Activation in T Lymphocytes: A Model of Differential Activation of Gene ExpressionAnnals of Biomedical Engineering, 2006
- The Transcription Factor NFAT3 Mediates Neuronal SurvivalOnline Journal of Public Health Informatics, 2005
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976