Modulation of glucocorticoid receptor induction properties by cofactors in peripheral blood mononuclear cells.
Glucocorticoids are widely used for their anti-inflammatory and immunosuppressive properties. Changing concentrations of transcriptional cofactors or chemicals in transiently transfected tissue culture cells modify several properties of glucocorticoid receptor-regulated gene expression including total activity (A(max)), agonist steroid potency (EC(50)), and the percentage of full agonist activity for antisteroids (percent partial agonist activity). However, no reports exist for endogenous genes in primary human cells. Here we document that reduced concentrations of TIF2, a p160 coactivator, in peripheral blood mononuclear cells modulate these parameters for endogenous genes in a gene-selective manner, thus establishing the physiological relevance of this behavior.
Luo
Min
M
Steroid Hormones Section, National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Endocrinology Branch, National Institutes of Health, Bethesda, MD 20892-1772, USA.
Simons
S Stoney
SS
D015870:Gene Expression / Q000502:physiology; D017930:Genes, Reporter / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000378:metabolism
C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D034741:RNA, Small Interfering; D011965:Receptors, Glucocorticoid