Glucocorticoid hormones upregulate interleukin 2 receptor alpha gene expression.
We present evidence that glucocorticoid hormones increase expression of IL-2Rec alpha chain on T cells by regulating IL-2Rec alpha gene transcription. We have previously reported that glucocorticoids can upregulate IL-2Rec alpha mRNA and protein expression in some T cell hybrids. In the present study we show that the glucocorticoid analogue dexamethasone increases mRNA levels of the endogenous IL-2Rec alpha gene and the expression of plasmids containing 5'-flanking sequences of the IL-2Rec alpha gene linked to CAT reporter genes transiently transfected into different cell lines. We show that the dexamethasone effect depends on cis-acting regulatory elements in a segment (-1835/-802) of the mouse gene that also contains cytokine response elements and a inducible DNase I-hypersensitive site. Dexamethasone responses of IL-2Rec alpha-CAT reporter gene constructs were observed in a CTL line, in an IL-3-dependent bone marrow-derived cell line, and in COS7 monkey kidney cells. In the latter the response depended on cotransfection of a glucocorticoid receptor expression vector. The biological relevance of the glucocorticoid-mediated upregulation of the IL-2Rec alpha gene is discussed.
Lamas
M
M
Centro de Investigaciones Biologicas, Madrid, Spain.
Sanz
E
E
Martin-Parras
L
L
Espel
E
E
Sperisen
P
P
Collins
M
M
Silva
A G
AG
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003850:Deoxyribonuclease I / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D017930:Genes, Reporter / Q000187:drug effects; D005938:Glucocorticoids / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000502:physiology
D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015375:Receptors, Interleukin-2; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase; D003850:Deoxyribonuclease I