0 10 Regulation regulation NN 11 13 of of IN 14 17 the the DT 18 23 human human JJ 24 37 interleukin-2 interleukin-2 NN 38 42 gene gene NN 43 45 by by IN 46 49 the the DT 50 55 alpha alpha NN 56 59 and and CC 60 64 beta beta NN 65 73 isoforms isoform NNS 74 76 of of IN 77 80 the the DT 81 95 glucocorticoid glucocorticoid NN 96 104 receptor receptor NN 104 105 . . . 107 110 The the DT 111 128 immunosuppressive immunosuppressive JJ 129 136 effects effect NNS 137 139 of of IN 140 155 glucocorticoids glucocorticoid NNS 156 159 are be VBP 160 167 largely largely RB 168 171 due due JJ 172 174 to to TO 175 190 transcriptional transcriptional JJ 191 201 inhibition inhibition NN 202 204 of of IN 205 220 immunologically immunologically RB 221 229 relevant relevant JJ 230 235 genes gene NNS 235 236 , , , 237 241 such such JJ 242 244 as as IN 245 248 the the DT 249 262 interleukin-2 interleukin-2 NN 263 264 ( ( ( 264 268 IL-2 il-2 NN 268 269 ) ) ) 270 274 gene gene NN 274 275 . . . 276 281 These these DT 282 289 effects effect NNS 290 293 are be VBP 294 302 mediated mediate VBN 303 305 by by IN 306 309 the the DT 310 323 intracellular intracellular JJ 324 338 glucocorticoid glucocorticoid NN 339 347 receptor receptor NN 348 349 ( ( ( 349 351 GR GR NNP 351 352 ) ) ) 352 353 . . . 354 356 In in IN 357 363 humans human NNS 363 364 , , , 365 376 alternative alternative JJ 377 385 splicing splicing NN 386 388 of of IN 389 392 the the DT 393 395 GR GR NNP 396 405 precursor precursor NN 406 410 mRNA mRNA NNP 411 416 gives give VBZ 417 421 rise rise NN 422 424 to to TO 425 428 two two CD 429 437 receptor receptor NN 438 446 isoforms isoform NNS 446 447 , , , 448 454 termed term VBN 455 462 GRalpha GRalpha NNP 463 466 and and CC 467 473 GRbeta GRbeta NNP 473 474 . . . 475 477 We we PRP 478 488 previously previously RB 489 501 demonstrated demonstrate VBD 502 506 that that IN 507 513 GRbeta GRbeta NNP 514 519 could could MD 520 530 antagonize antagonize VB 531 547 GRalpha-mediated gralpha-mediated JJ 548 563 transactivation transactivation NN 564 566 of of IN 567 568 a a DT 569 594 glucocorticoid-responsive glucocorticoid-responsive JJ 595 602 element element NN 603 604 ( ( ( 604 615 GRE)-driven gre)-driven JJ 616 624 reporter reporter NN 625 629 gene gene NN 630 632 in in IN 633 638 COS-7 cos-7 NN 639 644 cells cell NNS 644 645 . . . 646 649 The the DT 650 657 present present JJ 658 663 study study NN 664 667 was be VBD 668 676 designed design VBN 677 679 to to TO 680 687 analyze analyze VB 688 691 the the DT 692 697 roles role NNS 698 700 of of IN 701 704 the the DT 705 708 two two CD 709 711 GR gr NN 712 720 isoforms isoform NNS 721 723 on on IN 724 747 glucocorticoid-mediated glucocorticoid-mediated JJ 748 763 transrepression transrepression NN 764 766 of of IN 767 770 the the DT 771 775 IL-2 il-2 NN 776 780 gene gene NN 780 781 . . . 782 787 Using use VBG 788 789 a a DT 790 798 recently recently RB 799 808 developed develop VBN 809 821 transfection transfection NN 822 831 technique technique NN 831 832 , , , 833 835 we we PRP 836 847 demonstrate demonstrate VBP 848 852 that that IN 853 855 in in IN 856 863 primary primary JJ 864 869 human human JJ 870 881 lymphocytes lymphocyte NNS 881 882 , , , 883 894 stimulation stimulation NN 895 897 of of IN 898 899 a a DT 900 903 548 548 CD 904 906 bp bp NN 907 911 IL-2 il-2 NN 912 931 promoter-luciferase promoter-luciferase NN 932 940 reporter reporter NN 941 950 construct construct NN 951 953 by by IN 954 961 phorbol phorbol NN 962 967 ester ester NN 968 971 and and CC 972 979 calcium calcium NN 980 989 ionophore ionophore NN 990 992 is be VBZ 993 1001 reversed reverse VBN 1002 1004 by by IN 1005 1018 dexamethasone dexamethasone NN 1019 1021 to to TO 1022 1023 a a DT 1024 1031 similar similar JJ 1032 1038 extent extent NN 1039 1041 as as IN 1042 1044 in in IN 1045 1051 Jurkat Jurkat NNP 1052 1053 T t NN 1054 1062 lymphoma lymphoma NN 1063 1068 cells cell NNS 1069 1080 transfected transfecte VBN 1081 1085 with with IN 1086 1087 a a DT 1088 1095 GRalpha GRalpha NNP 1096 1106 expression expression NN 1107 1113 vector vector NN 1113 1114 . . . 1115 1127 Transfection transfection NN 1128 1130 of of IN 1131 1132 a a DT 1133 1139 GRbeta GRbeta NNP 1140 1150 expression expression NN 1151 1157 vector vector NN 1158 1163 alone alone RB 1164 1167 did do VBD 1168 1171 not not RB 1172 1178 result result VB 1179 1181 in in IN 1182 1186 IL-2 il-2 NN 1187 1195 promoter promoter NN 1196 1206 repression repression NN 1207 1209 in in IN 1210 1218 response response NN 1219 1221 to to TO 1222 1237 glucocorticoids glucocorticoid NNS 1237 1238 . . . 1239 1250 Furthermore furthermore RB 1250 1251 , , , 1252 1258 GRbeta GRbeta NNP 1259 1262 did do VBD 1263 1266 not not RB 1267 1277 antagonize antagonize VB 1278 1281 the the DT 1282 1292 repressive repressive JJ 1293 1300 effects effect NNS 1301 1303 of of IN 1304 1311 GRalpha GRalpha NNP 1312 1314 on on IN 1315 1319 IL-2 il-2 NN 1320 1328 promoter promoter NN 1329 1337 activity activity NN 1337 1338 . . . 1339 1351 Surprisingly surprisingly RB 1351 1352 , , , 1353 1367 overexpression overexpression NN 1368 1370 of of IN 1371 1377 GRbeta GRbeta NNP 1378 1380 in in IN 1381 1387 Jurkat Jurkat NNP 1388 1393 cells cell NNS 1394 1397 did do VBD 1398 1401 not not RB 1402 1407 cause cause VB 1408 1419 significant significant JJ 1420 1430 inhibition inhibition NN 1431 1433 of of IN 1434 1449 GRalpha-induced gralpha-induced JJ 1450 1465 transactivation transactivation NN 1466 1468 of of IN 1469 1470 a a DT 1471 1484 GRE-dependent gre-dependent JJ 1485 1495 luciferase luciferase NN 1496 1504 reporter reporter NN 1505 1509 gene gene NN 1510 1516 either either RB 1516 1517 . . . 1518 1520 We we PRP 1521 1529 conclude conclude VBP 1530 1534 that that IN 1535 1538 the the DT 1539 1554 transrepressive transrepressive JJ 1555 1561 effect effect NN 1562 1564 of of IN 1565 1580 glucocorticoids glucocorticoid NNS 1581 1583 on on IN 1584 1588 IL-2 il-2 NN 1589 1593 gene gene NN 1594 1607 transcription transcription NN 1608 1610 is be VBZ 1611 1622 exclusively exclusively RB 1623 1631 mediated mediate VBN 1632 1634 by by IN 1635 1642 GRalpha GRalpha NNP 1642 1643 . . . 1644 1650 GRbeta GRbeta NNP 1651 1654 can can MD 1655 1662 neither neither CC 1663 1673 antagonize antagonize VB 1674 1690 GRalpha-mediated gralpha-mediated JJ 1691 1706 transactivation transactivation NN 1707 1710 nor nor CC 1711 1726 transrepression transrepression NN 1727 1729 in in IN 1730 1736 Jurkat Jurkat NNP 1737 1742 cells cell NNS 1742 1743 , , , 1744 1754 indicating indicate VBG 1755 1756 a a DT 1757 1761 cell cell NN 1762 1775 type-specific type-specific JJ 1776 1783 pattern pattern NN 1784 1786 of of IN 1787 1802 GRbeta-mediated grbeta-mediated JJ 1803 1821 antiglucocorticoid antiglucocorticoid NN 1822 1830 activity activity NN 1830 1831 . . .