[Effect of dexamethasone on the human interleukin-2 receptor alpha chain gene expression].
Glucocorticoids have wide effects on the immune system, the mechanisms of these effects have not been clearly defined. The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) is a critical control point in the T-cell mediated immune response. The effect of dexamethasone, a synthetic glucocorticoid hormone, on IL-2R is unclear in comparison with its inhibition on the accumulation of IL-2 mRNA. Our study shows that dexamethasone increases the basal and PHA-induced mRNA levels of IL-2R alpha gene in Jurkat cells, but it does not affect the expression of reporter gene constructs containing 5' flanking sequences (-482bp/ +16bp or -350bp/+16bp) of the IL-2R alpha gene in PHA activated Jurkat cells. These results indicate that dexamethasone plays a positive regulatory role in the IL-2R alpha gene expression, but the effect is not mediated by the previously identified proximal regulatory elements located between -482bp/+1bp. Meanwhile, our results also provide evidence that the activation mechanism of dexamethasone is different from that of PHA, and that dexamethasone and PHA show a synergistic effect in the induction of IL-2R alpha gene expression.
Guan
Z
Z
Institute of Basic Medical Sciences, CAMS and PUMC, Beijing.
Wu
N
N
Shen
Y
Y
D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism
D005938:Glucocorticoids; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D003907:Dexamethasone