0 10 Regulation regulation NN 11 13 of of IN 14 27 interleukin-2 interleukin-2 NN 28 36 receptor receptor NN 37 42 alpha alpha NN 43 48 chain chain NN 49 59 expression expression NN 60 63 and and CC 64 71 nuclear nuclear JJ 72 84 factor.kappa factor.kappa NN 85 86 B B NNP 87 97 activation activation NN 98 100 by by IN 101 108 protein protein NN 109 115 kinase kinase NNP 116 117 C C NNP 118 120 in in IN 121 122 T t NN 123 134 lymphocytes lymphocyte NNS 134 135 . . . 136 145 Autocrine Autocrine NNP 146 150 role role NN 151 153 of of IN 154 159 tumor tumor NN 160 168 necrosis necrosis NN 169 175 factor factor NN 176 181 alpha alpha NN 181 182 . . . 184 187 The the DT 188 198 regulation regulation NN 199 201 of of IN 202 215 interleukin-2 interleukin-2 NN 216 224 receptor receptor NN 225 230 alpha alpha NN 231 236 chain chain NN 237 238 ( ( ( 238 243 IL-2R IL-2R NNP 244 249 alpha alpha NN 249 250 ) ) ) 251 261 expression expression NN 262 265 and and CC 266 273 nuclear nuclear JJ 274 280 factor factor NN 281 282 ( ( ( 282 284 NF NF NNP 284 285 ) ) ) 286 296 activation activation NN 297 299 by by IN 300 307 protein protein NN 308 314 kinase kinase NNP 315 316 C C NNP 317 318 ( ( ( 318 321 PKC PKC NNP 321 322 ) ) ) 323 325 in in IN 326 333 resting rest VBG 334 335 T t NN 336 341 cells cell NNS 341 342 , , , 343 346 has have VBZ 347 351 been be VBN 352 359 studied study VBN 359 360 . . . 361 370 Treatment Treatment NNP 371 373 of of IN 374 379 human human JJ 380 387 resting rest VBG 388 389 T t NN 390 395 cells cell NNS 396 400 with with IN 401 408 phorbol phorbol NN 409 415 esters ester NNS 416 424 strongly strongly RB 425 432 induced induce VBD 433 436 the the DT 437 447 expression expression NN 448 450 of of IN 451 456 IL-2R IL-2R NNP 457 462 alpha alpha NN 463 466 and and CC 467 470 the the DT 471 481 activation activation NN 482 484 of of IN 485 493 NF.kappa NF.kappa NNP 494 496 B. B. NNP 497 501 This this DT 502 512 activation activation NN 513 516 was be VBD 517 520 due due JJ 521 523 to to TO 524 527 the the DT 528 541 translocation translocation NN 542 544 of of IN 545 548 p65 p65 NN 549 552 and and CC 553 558 c-Rel c-rel NN 559 567 NF.kappa NF.kappa NNP 568 569 B B NNP 570 578 proteins protein NNS 579 583 from from IN 584 595 cytoplasmic cytoplasmic JJ 596 602 stores store NNS 603 605 to to TO 606 609 the the DT 610 617 nucleus nucleus NN 617 618 , , , 619 624 where where WRB 625 629 they they PRP 630 635 bound bind VBD 636 639 the the DT 640 645 kappa kappa NN 646 647 B B NNP 648 656 sequence sequence NN 657 659 of of IN 660 663 the the DT 664 669 IL-2R IL-2R NNP 670 675 alpha alpha NN 676 684 promoter promoter NN 685 691 either either CC 692 694 as as IN 695 702 p50.p65 p50.p65 NN 703 705 or or CC 706 708 as as IN 709 718 p50.c-Rel p50.c-rel NN 719 731 heterodimers heterodimer NNS 731 732 . . . 733 746 Interestingly interestingly RB 746 747 , , , 748 751 all all DT 752 754 of of IN 755 760 those those DT 761 767 events event NNS 768 772 were be VBD 773 780 largely largely RB 781 789 indirect indirect JJ 790 793 and and CC 794 802 mediated mediate VBN 803 805 by by IN 806 818 endogenously endogenously RB 819 827 secreted secrete VBN 828 833 tumor tumor NN 834 842 necrosis necrosis NN 843 849 factor factor NN 850 855 alpha alpha NN 856 857 ( ( ( 857 860 TNF TNF NNP 861 866 alpha alpha NN 866 867 ) ) ) 867 868 , , , 869 871 as as IN 872 876 they they PRP 877 881 were be VBD 882 890 strongly strongly RB 891 900 inhibited inhibit VBN 901 903 by by IN 904 905 a a DT 906 918 neutralizing neutralize VBG 919 927 anti-TNF anti-tnf JJ 928 933 alpha alpha NN 934 944 monoclonal monoclonal JJ 945 953 antibody antibody NN 953 954 . . . 955 966 Furthermore furthermore RB 966 967 , , , 968 979 cyclosporin cyclosporin NN 980 981 A A NNP 981 982 , , , 983 988 which which WDT 989 996 blocked block VBD 997 1000 TNF TNF NNP 1001 1006 alpha alpha NN 1007 1017 production production NN 1018 1025 induced induce VBN 1026 1028 by by IN 1029 1032 PKC PKC NNP 1032 1033 , , , 1034 1042 strongly strongly RB 1043 1052 inhibited inhibit VBD 1053 1058 IL-2R IL-2R NNP 1059 1064 alpha alpha NN 1065 1068 and and CC 1069 1077 NF.kappa NF.kappa NNP 1078 1079 B B NNP 1080 1090 activation activation NN 1090 1091 . . . 1092 1095 The the DT 1096 1104 addition addition NN 1105 1107 of of IN 1108 1114 either either CC 1115 1118 TNF TNF NNP 1119 1124 alpha alpha NN 1125 1127 or or CC 1128 1132 IL-2 il-2 NN 1133 1142 partially partially RB 1143 1152 recovered recover VBD 1153 1164 cyclosporin cyclosporin NN 1165 1174 A-induced a-induced JJ 1175 1180 IL-2R IL-2R NNP 1181 1186 alpha alpha NN 1187 1197 inhibition inhibition NN 1197 1198 , , , 1199 1202 but but CC 1203 1207 only only RB 1208 1211 TNF TNF NNP 1212 1217 alpha alpha NN 1218 1228 completely completely RB 1229 1238 recovered recover VBD 1239 1247 NF.kappa NF.kappa NNP 1248 1249 B B NNP 1250 1260 activation activation NN 1260 1261 . . . 1262 1267 Those those DT 1268 1275 results result NNS 1276 1284 indicate indicate VBP 1285 1289 that that IN 1289 1290 , , , 1291 1293 in in IN 1294 1301 resting rest VBG 1302 1303 T t NN 1304 1309 cells cell NNS 1309 1310 , , , 1311 1314 PKC PKC NNP 1315 1325 activation activation NN 1326 1329 has have VBZ 1330 1334 only only RB 1335 1336 a a DT 1337 1347 triggering trigger VBG 1348 1352 role role NN 1352 1353 , , , 1354 1361 whereas whereas IN 1362 1365 the the DT 1366 1378 endogenously endogenously RB 1379 1387 secreted secrete VBN 1388 1391 TNF TNF NNP 1392 1397 alpha alpha NN 1398 1403 plays play VBZ 1404 1406 an an DT 1407 1416 essential essential JJ 1417 1421 role role NN 1422 1424 in in IN 1425 1428 the the DT 1429 1441 quantitative quantitative JJ 1442 1449 control control NN 1450 1452 of of IN 1453 1456 the the DT 1457 1467 expression expression NN 1468 1470 of of IN 1471 1476 IL-2R IL-2R NNP 1477 1482 alpha alpha NN 1483 1488 chain chain NN 1489 1491 or or CC 1492 1500 NF.kappa NF.kappa NNP 1501 1502 B B NNP 1503 1513 activation activation NN 1513 1514 . . .