0 8 Negative negative JJ 9 24 transcriptional transcriptional JJ 25 35 regulation regulation NN 36 38 of of IN 39 44 human human JJ 45 56 interleukin interleukin NN 57 58 2 2 CD 59 60 ( ( ( 60 64 IL-2 il-2 NN 64 65 ) ) ) 66 70 gene gene NN 71 73 by by IN 74 89 glucocorticoids glucocorticoid NNS 90 97 through through IN 98 110 interference interference NN 111 115 with with IN 116 123 nuclear nuclear JJ 124 137 transcription transcription NN 138 145 factors factor NNS 146 150 AP-1 ap-1 NN 151 154 and and CC 155 160 NF-AT NF-AT NNP 160 161 . . . 163 167 IL-2 il-2 NN 168 172 gene gene NN 173 186 transcription transcription NN 187 189 is be VBZ 190 198 affected affect VBN 199 201 by by IN 202 209 several several JJ 210 217 nuclear nuclear JJ 218 226 proteins protein NNS 226 227 . . . 228 230 We we PRP 231 236 asked ask VBD 237 244 whether whether IN 245 258 dexamethasone dexamethasone NN 259 260 ( ( ( 260 263 Dex Dex NNP 263 264 ) ) ) 265 268 and and CC 269 280 cyclosporin cyclosporin NN 281 282 A a NN 283 284 ( ( ( 284 287 CsA CsA NNP 287 288 ) ) ) 289 296 inhibit inhibit VBP 297 301 IL-2 il-2 NN 302 306 gene gene NN 307 320 transcription transcription NN 321 323 by by IN 324 335 interfering interfere VBG 336 340 with with IN 341 344 the the DT 345 353 activity activity NN 354 356 of of IN 357 364 nuclear nuclear JJ 365 373 proteins protein NNS 374 378 that that WDT 379 383 bind bind VBP 384 386 to to TO 387 390 the the DT 391 395 IL-2 il-2 NN 396 404 promoter promoter NN 404 405 . . . 406 413 Nuclear nuclear JJ 414 422 extracts extract NNS 423 427 from from IN 428 435 primary primary JJ 436 441 human human JJ 442 443 T t NN 444 455 lymphocytes lymphocyte NNS 456 460 were be VBD 461 469 analyzed analyze VBN 470 472 by by IN 473 488 electrophoretic electrophoretic JJ 489 492 DNA dna NN 493 501 mobility mobility NN 502 507 shift shift NN 508 514 assays assay NNS 514 515 . . . 516 520 Both both CC 521 524 Dex Dex NNP 525 528 and and CC 529 532 CsA CsA NNP 533 542 inhibited inhibit VBD 543 546 the the DT 547 554 binding binding NN 555 557 of of IN 558 571 transcription transcription NN 572 579 factors factor NNS 580 584 AP-1 ap-1 NN 585 588 and and CC 589 594 NF-AT NF-AT NNP 594 595 , , , 596 599 but but CC 600 603 not not RB 604 606 of of IN 607 612 NF-kB NF-kB NNP 613 616 and and CC 617 626 OCT-1/OAF OCT-1/OAF NNP 626 627 , , , 628 630 to to TO 631 636 their their PRP$ 637 650 corresponding correspond VBG 651 656 sites site NNS 657 659 on on IN 660 663 the the DT 664 668 IL-2 il-2 NN 669 673 gene gene NN 674 682 promoter promoter NN 682 683 . . . 684 686 To to TO 687 696 correlate correlate VB 697 704 changes change NNS 705 707 in in IN 708 715 nuclear nuclear JJ 716 722 factor factor NN 723 730 binding binding NN 731 733 in in FW 734 739 vitro vitro FW 740 744 with with IN 745 760 transcriptional transcriptional JJ 761 769 activity activity NN 770 772 in in FW 773 777 vivo vivo FW 778 781 and and CC 782 788 define define VB 789 792 the the DT 793 803 structural structural JJ 804 816 requirements requirement NNS 817 820 for for IN 821 825 IL-2 il-2 NN 826 834 promoter promoter NN 835 845 repression repression NN 845 846 , , , 847 849 we we PRP 850 854 used use VBD 855 864 transient transient JJ 865 868 DNA dna NN 869 882 transfections transfection NNS 882 883 . . . 884 890 Jurkat Jurkat NNP 891 896 cells cell NNS 897 901 were be VBD 902 913 transfected transfecte VBN 914 918 with with IN 919 927 plasmids plasmid NNS 928 938 containing contain VBG 939 945 either either CC 946 949 the the DT 950 956 intact intact JJ 957 961 IL-2 il-2 NN 962 970 promoter promoter NN 971 973 or or CC 974 977 its its PRP$ 978 982 AP-1 ap-1 NN 982 983 , , , 984 989 NF-AT NF-AT NNP 989 990 , , , 991 994 and and CC 995 1000 NF-kB NF-kB NNP 1001 1007 motifs motif NNS 1007 1008 . . . 1009 1012 Dex Dex NNP 1013 1022 inhibited inhibit VBD 1023 1026 the the DT 1027 1031 IL-2 il-2 NN 1032 1040 promoter promoter NN 1041 1044 and and CC 1045 1048 the the DT 1049 1053 AP-1 ap-1 NN 1053 1054 , , , 1055 1058 but but CC 1059 1062 not not RB 1063 1066 the the DT 1067 1072 NF-AT NF-AT NNP 1073 1076 and and CC 1077 1082 NF-kB NF-kB NNP 1083 1091 plasmids plasmid NNS 1091 1092 . . . 1093 1095 In in IN 1096 1104 contrast contrast NN 1104 1105 , , , 1106 1109 CsA CsA NNP 1110 1119 inhibited inhibit VBD 1120 1123 the the DT 1124 1128 IL-2 il-2 NN 1129 1137 promoter promoter NN 1138 1141 and and CC 1142 1145 the the DT 1146 1151 NF-AT NF-AT NNP 1151 1152 , , , 1153 1156 but but CC 1157 1160 not not RB 1161 1164 the the DT 1165 1169 AP-1 ap-1 NN 1170 1173 and and CC 1174 1179 NF-kB nf-kb NN 1180 1188 plasmids plasmid NNS 1188 1189 . . . 1190 1195 These these DT 1196 1203 results result NNS 1204 1211 suggest suggest VBP 1212 1216 that that IN 1217 1219 in in IN 1220 1225 human human JJ 1226 1227 T t NN 1228 1239 lymphocytes lymphocyte NNS 1240 1244 both both CC 1245 1248 Dex Dex NNP 1249 1252 and and CC 1253 1256 CsA CsA NNP 1257 1266 inhibited inhibit VBD 1267 1271 IL-2 il-2 NN 1272 1276 gene gene NN 1277 1290 transcription transcription NN 1291 1298 through through IN 1299 1311 interference interference NN 1312 1316 with with IN 1317 1330 transcription transcription NN 1331 1338 factors factor NNS 1339 1343 AP-1 ap-1 NN 1344 1347 and and CC 1348 1353 NF-AT NF-AT NNP 1353 1354 . . . 1355 1357 We we PRP 1358 1365 propose propose VBP 1366 1370 that that IN 1370 1371 , , , 1372 1377 while while IN 1378 1385 maximum maximum JJ 1386 1396 inhibition inhibition NN 1397 1400 may may MD 1401 1408 involve involve VB 1409 1420 interaction interaction NN 1421 1425 with with IN 1426 1430 both both DT 1431 1444 transcription transcription NN 1445 1452 factors factor NNS 1452 1453 , , , 1454 1458 AP-1 ap-1 NN 1459 1461 is be VBZ 1462 1465 the the DT 1466 1473 primary primary JJ 1474 1480 target target NN 1481 1483 of of IN 1484 1487 Dex Dex NNP 1487 1488 . . .