title: Glucocorticoids regulate natural killer cell function epigenetically.
abstract: Although glucocorticoids are well known for their capacity to suppress the immune response, glucocorticoids can also promote immune responsiveness. It was the purpose of this investigation to evaluate the molecular basis for this apparent dichotomous immunologic effect. Glucocorticoid treatment of natural killer cells (NK) was shown to reduce NK cell cytolytic activity by reduction of histone promoter acetylation for perforin and granzyme B, which corresponded with reduced mRNA and protein for each. In contrast, glucocorticoid treatment increased histone acetylation at regulatory regions for interferon gamma and IL-6, as well as chromatin accessibility for each. This increase in histone acetylation was associated with increased proinflammatory cytokine mRNA and protein production upon cellular stimulation. These immunologic effects were evident at the level of the individual cell and demonstrate glucocorticoids to epigenetically reduce NK cell cytolytic activity while at the same time to prime NK cells for proinflammatory cytokine production.
authors: Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153, USA.
authors: Justin L
authors: JL
authors: Eddy
authors: Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153, USA.
authors: Karen
authors: K
authors: Krukowski
authors: Marcella Niehoff School of Nursing, Loyola University of Chicago, Maywood, IL 60153, USA.
authors: Linda
authors: L
authors: Janusek
authors: Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153, USA. Electronic address: hmathew@lumc.edu.
authors: Herbert L
authors: HL
authors: Mathews
mesh_terms: D000107:Acetylation; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D054353:Perforin / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000096:biosynthesis
chemical_list: D002843:Chromatin; D005938:Glucocorticoids; D006657:Histones; C508600:IL6 protein, human; D015850:Interleukin-6; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; C498143:RELA protein, human; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D054353:Perforin; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes
keywords: Epigenetic; Glucocorticoids; Granule constituents; Natural killer cells; Proinflammatory cytokines