0 10 Inhibition Inhibition NNP 11 13 of of IN 14 29 NF-AT-dependent nf-at-dependent JJ 30 43 transcription transcription NN 44 46 by by IN 47 55 NF-kappa NF-kappa NNP 56 57 B B NNP 57 58 : : : 59 71 implications implication NNS 72 75 for for IN 76 88 differential differential JJ 89 93 gene gene NN 94 104 expression expression NN 105 107 in in IN 108 109 T t NN 110 116 helper helper NN 117 121 cell cell NN 122 129 subsets subset NNS 129 130 . . . 132 142 Activation Activation NNP 143 145 of of IN 146 156 individual individual JJ 157 161 CD4+ cd4+ JJ 162 163 T t NN 164 169 cells cell NNS 170 177 results result VBZ 178 180 in in IN 181 193 differential differential JJ 194 204 lymphokine lymphokine NN 205 215 expression expression NN 215 216 : : : 217 228 interleukin interleukin NN 229 230 2 2 CD 231 232 ( ( ( 232 236 IL-2 il-2 NN 236 237 ) ) ) 238 240 is be VBZ 241 255 preferentially preferentially RB 256 264 produced produce VBN 265 267 by by IN 268 269 T t NN 270 276 helper helper NN 277 281 type type NN 282 283 1 1 CD 284 285 ( ( ( 285 288 TH1 th1 NN 288 289 ) ) ) 290 295 cells cell NNS 295 296 , , , 297 302 which which WDT 303 306 are be VBP 307 315 involved involve VBN 316 318 in in IN 319 332 cell-mediated cell-mediated JJ 333 339 immune immune JJ 340 349 responses response NNS 349 350 , , , 351 358 whereas whereas IN 359 363 IL-4 il-4 NN 364 366 is be VBZ 367 378 synthesized synthesize VBN 379 381 by by IN 382 385 TH2 th2 NN 386 391 cells cell NNS 391 392 , , , 393 398 which which WDT 399 402 are be VBP 403 412 essential essential JJ 413 416 for for IN 417 424 humoral humoral JJ 425 433 immunity immunity NN 433 434 . . . 435 438 The the DT 439 455 Ca(2+)-dependent ca(2+)-dependent JJ 456 462 factor factor NN 463 469 NF-ATp NF-ATp NNP 470 475 plays play VBZ 476 477 a a DT 478 481 key key JJ 482 486 role role NN 487 489 in in IN 490 493 the the DT 494 503 inducible inducible JJ 504 517 transcription transcription NN 518 520 of of IN 521 525 both both DT 526 531 these these DT 532 542 lymphokine lymphokine NN 543 548 genes gene NNS 548 549 . . . 550 557 However however RB 557 558 , , , 559 564 while while IN 565 568 IL2 il2 NN 569 579 expression expression NN 580 588 requires require VBZ 589 592 the the DT 593 605 contribution contribution NN 606 608 of of IN 609 616 Ca(2+)- ca(2+)- NN 617 620 and and CC 621 628 protein protein NN 629 635 kinase kinase NNP 636 647 C-dependent c-dependent JJ 648 655 signals signal NNS 655 656 , , , 657 659 we we PRP 660 666 report report VBP 667 671 that that IN 672 682 activation activation NN 683 685 of of IN 686 691 human human JJ 692 695 IL4 il4 NN 696 709 transcription transcription NN 710 717 through through IN 718 721 the the DT 722 738 Ca(2+)-dependent ca(2+)-dependent JJ 739 746 pathway pathway NN 747 749 is be VBZ 750 760 diminished diminish VBN 761 763 by by IN 764 771 protein protein NN 772 778 kinase kinase NNP 779 780 C C NNP 781 792 stimulation stimulation NN 793 795 in in IN 796 802 Jurkat Jurkat NNP 803 804 T t NN 805 810 cells cell NNS 810 811 . . . 812 816 This this DT 817 827 phenomenon phenomenon NN 828 830 is be VBZ 831 834 due due IN 835 837 to to TO 838 846 mutually mutually RB 847 856 exclusive exclusive JJ 857 864 binding binding NN 865 867 of of IN 868 874 NF-ATp NF-ATp NNP 875 878 and and CC 879 887 NF-kappa NF-kappa NNP 888 889 B B NNP 890 892 to to TO 893 896 the the DT 897 898 P p NN 899 907 sequence sequence NN 907 908 , , , 909 911 an an DT 912 919 element element NN 920 927 located located JJ 928 930 69 69 CD 931 933 bp bp NN 934 942 upstream upstream RB 943 945 of of IN 946 949 the the DT 950 953 IL4 il4 NN 954 967 transcription transcription NN 968 978 initiation initiation NN 979 983 site site NN 983 984 . . . 985 990 Human human JJ 991 994 IL4 IL4 NNP 995 1012 promoter-mediated promoter-mediated JJ 1013 1026 transcription transcription NN 1027 1029 is be VBZ 1030 1043 downregulated downregulate VBN 1044 1046 in in IN 1047 1053 Jurkat Jurkat NNP 1054 1059 cells cell NNS 1060 1070 stimulated stimulate VBN 1071 1075 with with IN 1076 1079 the the DT 1080 1088 NF-kappa NF-kappa NNP 1089 1101 B-activating b-activating JJ 1102 1110 cytokine cytokine NN 1111 1116 tumor tumor NN 1117 1125 necrosis necrosis NN 1126 1132 factor factor NN 1133 1138 alpha alpha NN 1139 1142 and and CC 1143 1153 suppressed suppress VBD 1154 1156 in in IN 1157 1176 RelA-overexpressing rela-overexpressing JJ 1177 1182 cells cell NNS 1182 1183 . . . 1184 1186 In in IN 1187 1195 contrast contrast NN 1195 1196 , , , 1197 1204 protein protein NN 1205 1211 kinase kinase NNP 1212 1213 C C NNP 1214 1225 stimulation stimulation NN 1226 1228 or or CC 1229 1233 RelA RelA NNP 1234 1248 overexpression overexpression NN 1249 1253 does do VBZ 1254 1257 not not RB 1258 1264 affect affect VB 1265 1268 the the DT 1269 1277 activity activity NN 1278 1280 of of IN 1281 1282 a a DT 1283 1288 human human JJ 1289 1292 IL4 il4 NN 1293 1301 promoter promoter NN 1302 1312 containing contain VBG 1313 1314 a a DT 1315 1320 mouse mouse NN 1321 1322 P p NN 1323 1331 sequence sequence NN 1331 1332 , , , 1333 1338 which which WDT 1339 1341 is be VBZ 1342 1343 a a DT 1344 1359 higher-affinity higher-affinity JJ 1360 1364 site site NN 1365 1368 for for IN 1369 1375 NF-ATp NF-ATp NNP 1376 1379 and and CC 1380 1381 a a DT 1382 1396 lower-affinity lower-affinity JJ 1397 1401 site site NN 1402 1405 for for IN 1406 1410 RelA RelA NNP 1410 1411 . . . 1412 1416 Thus thus RB 1416 1417 , , , 1418 1429 competition competition NN 1430 1437 between between IN 1438 1441 two two CD 1442 1449 general general JJ 1450 1465 transcriptional transcriptional JJ 1466 1476 activators activator NNS 1476 1477 , , , 1478 1482 RelA RelA NNP 1483 1486 and and CC 1487 1493 NF-ATp NF-ATp NNP 1493 1494 , , , 1495 1503 mediates mediate VBZ 1504 1507 the the DT 1508 1518 inhibitory inhibitory JJ 1519 1525 effect effect NN 1526 1528 of of IN 1529 1536 protein protein NN 1537 1543 kinase kinase NNP 1544 1545 C C NNP 1546 1557 stimulation stimulation NN 1558 1560 on on IN 1561 1564 IL4 il4 NN 1565 1575 expression expression NN 1576 1579 and and CC 1580 1583 may may MD 1584 1594 contribute contribute VB 1595 1597 to to TO 1598 1610 differential differential JJ 1611 1615 gene gene NN 1616 1626 expression expression NN 1627 1629 in in IN 1630 1632 TH th NN 1633 1638 cells cell NNS 1638 1639 . . .