title: Glucocorticoid receptor mediated suppression of natural killer cell activity: identification of associated deacetylase and corepressor molecules.
abstract: Physical and psychological stressors reduce natural killer cell function. This reduction in cellular function results from stress-induced release of glucocorticoids. Glucocorticoids act upon natural killer cells to deacetylate and transrepress immune response genes through epigenetic processes. However, other than the glucocorticoid receptor, the proteins that participate in this process are not well described in natural killer cells. The purpose of this study was to identify the proteins associated with the glucocorticoid receptor that are likely epigenetic participants in this process. Treatment of natural killer cells with the synthetic glucocorticoid, dexamethasone, produced a significant time dependent reduction in natural killer cell activity as early as 8h post treatment. This reduction in natural killer cell activity was preceded by nuclear localization of the glucocorticoid receptor with histone deacetylase 1 and the corepressor, SMRT. Other class I histone deacetylases were not associated with the glucocorticoid receptor nor was the corepressor NCoR. These results demonstrate histone deacetylase 1 and SMRT to associate with the ligand activated glucocorticoid receptor within the nuclei of natural killer cells and to be the likely participants in the histone deacetylation and transrepression that accompanies glucocorticoid mediated reductions in natural killer cell function.
authors.affiliation: Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153, USA.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Bush
authors.forename: Karen
authors.initials: K
authors.lastname: Krukowski
authors.forename: Justin L
authors.initials: JL
authors.lastname: Eddy
authors.forename: Linda Witek
authors.initials: LW
authors.lastname: Janusek
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Mathews
mesh_terms: D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D006655:Histone Deacetylases / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D011965:Receptors, Glucocorticoid / Q000276:immunology*
chemical_list: D056970:Co-Repressor Proteins; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D006655:Histone Deacetylases