0 8 Abnormal abnormal JJ 9 17 NF-kappa NF-kappa NNP 18 19 B B NNP 20 28 activity activity NN 29 31 in in IN 32 33 T t NN 34 45 lymphocytes lymphocyte NNS 46 50 from from IN 51 59 patients patient NNS 60 64 with with IN 65 73 systemic systemic JJ 74 79 lupus lupus NN 80 93 erythematosus erythematosus NN 94 96 is be VBZ 97 107 associated associate VBN 108 112 with with IN 113 122 decreased decrease VBN 123 131 p65-RelA p65-rela NN 132 139 protein protein NN 140 150 expression expression NN 150 151 . . . 153 161 Numerous numerous JJ 162 170 cellular cellular JJ 171 174 and and CC 175 186 biochemical biochemical JJ 187 200 abnormalities abnormality NNS 201 203 in in IN 204 210 immune immune JJ 211 221 regulation regulation NN 222 226 have have VBP 227 231 been be VBN 232 241 described describe VBN 242 244 in in IN 245 253 patients patient NNS 254 258 with with IN 259 267 systemic systemic JJ 268 273 lupus lupus NN 274 287 erythematosus erythematosus NN 288 289 ( ( ( 289 292 SLE SLE NNP 292 293 ) ) ) 293 294 , , , 295 304 including include VBG 305 312 surface surface NN 313 315 Ag ag NN 316 334 receptor-initiated receptor-initiated JJ 335 344 signaling signaling NN 345 351 events event NNS 352 355 and and CC 356 366 lymphokine lymphokine NN 367 377 production production NN 377 378 . . . 379 386 Because because IN 387 395 NF-kappa NF-kappa NNP 396 397 B B NNP 398 409 contributes contribute VBZ 410 412 to to TO 413 416 the the DT 417 430 transcription transcription NN 431 433 of of IN 434 442 numerous numerous JJ 443 455 inflammatory inflammatory JJ 456 461 genes gene NNS 462 465 and and CC 466 469 has have VBZ 470 474 been be VBN 475 480 shown show VBN 481 483 to to TO 484 486 be be VB 487 488 a a DT 489 498 molecular molecular JJ 499 505 target target NN 506 508 of of IN 509 525 antiinflammatory antiinflammatory JJ 526 531 drugs drug NNS 531 532 , , , 533 535 we we PRP 536 542 sought seek VBD 543 545 to to TO 546 558 characterize characterize VB 559 562 the the DT 563 573 functional functional JJ 574 578 role role NN 579 581 of of IN 582 585 the the DT 586 594 NF-kappa NF-kappa NNP 595 596 B B NNP 597 604 protein protein NN 605 612 complex complex NN 613 615 in in IN 616 621 lupus lupus NN 622 623 T t NN 624 629 cells cell NNS 629 630 . . . 631 638 Freshly freshly RB 639 647 isolated isolate VBN 648 649 T t NN 650 655 cells cell NNS 656 660 from from IN 661 666 lupus lupus NN 667 675 patients patient NNS 675 676 , , , 677 687 rheumatoid rheumatoid JJ 688 697 arthritis arthritis NN 698 699 ( ( ( 699 701 RA RA NNP 701 702 ) ) ) 703 711 patients patient NNS 711 712 , , , 713 716 and and CC 717 723 normal normal JJ 724 735 individuals individual NNS 736 740 were be VBD 741 750 activated activate VBN 751 766 physiologically physiologically RB 767 770 via via IN 771 774 the the DT 775 778 TCR TCR NNP 779 783 with with IN 784 792 anti-CD3 anti-cd3 JJ 793 796 and and CC 797 806 anti-CD28 anti-cd28 JJ 807 810 Abs ab NNS 811 813 to to TO 814 820 assess assess VB 821 829 proximal proximal JJ 830 838 membrane membrane NN 839 848 signaling signaling NN 848 849 , , , 850 853 and and CC 854 858 with with IN 859 862 PMA PMA NNP 863 866 and and CC 867 868 a a DT 869 876 calcium calcium NN 877 886 ionophore ionophore NN 887 888 ( ( ( 888 894 A23187 A23187 NNP 894 895 ) ) ) 896 898 to to TO 899 905 bypass bypass VB 906 923 membrane-mediated membrane-mediated JJ 924 933 signaling signaling NN 934 940 events event NNS 940 941 . . . 942 944 We we PRP 945 953 measured measure VBD 954 957 the the DT 958 966 NF-kappa NF-kappa NNP 967 968 B B NNP 969 976 binding binding NN 977 985 activity activity NN 986 988 in in IN 989 996 nuclear nuclear JJ 997 1005 extracts extract NNS 1006 1008 by by IN 1009 1012 gel gel NN 1013 1018 shift shift NN 1019 1027 analysis analysis NN 1027 1028 . . . 1029 1033 When when WRB 1034 1042 compared compare VBN 1043 1047 with with IN 1048 1054 normal normal JJ 1055 1060 cells cell NNS 1060 1061 , , , 1062 1065 the the DT 1066 1076 activation activation NN 1077 1079 of of IN 1080 1088 NF-kappa NF-kappa NNP 1089 1090 B B NNP 1091 1099 activity activity NN 1100 1102 in in IN 1103 1106 SLE SLE NNP 1107 1115 patients patient NNS 1116 1119 was be VBD 1120 1133 significantly significantly RB 1134 1143 decreased decrease VBN 1144 1146 in in IN 1147 1150 SLE SLE NNP 1150 1151 , , , 1152 1155 but but CC 1156 1159 not not RB 1160 1162 in in IN 1163 1165 RA RA NNP 1165 1166 , , , 1167 1175 patients patient NNS 1175 1176 . . . 1177 1185 NF-kappa NF-kappa NNP 1186 1187 B B NNP 1188 1195 binding binding NN 1196 1204 activity activity NN 1205 1208 was be VBD 1209 1215 absent absent JJ 1216 1218 in in IN 1219 1226 several several JJ 1227 1230 SLE sle NN 1231 1239 patients patient NNS 1240 1243 who who WP 1244 1248 were be VBD 1249 1252 not not RB 1253 1262 receiving receive VBG 1263 1266 any any DT 1267 1277 medication medication NN 1277 1278 , , , 1279 1288 including include VBG 1289 1304 corticosteroids corticosteroid NNS 1304 1305 . . . 1306 1310 Also also RB 1310 1311 , , , 1312 1320 NF-kappa NF-kappa NNP 1321 1322 B B NNP 1323 1331 activity activity NN 1332 1340 remained remain VBD 1341 1347 absent absent JJ 1348 1350 in in IN 1351 1360 follow-up follow-up JJ 1361 1368 studies study NNS 1368 1369 . . . 1370 1372 In in IN 1373 1383 supershift supershift NN 1384 1395 experiments experiment NNS 1396 1401 using use VBG 1402 1410 specific specific JJ 1411 1414 Abs ab NNS 1414 1415 , , , 1416 1418 we we PRP 1419 1425 showed show VBD 1426 1430 that that IN 1430 1431 , , , 1432 1434 in in IN 1435 1438 the the DT 1439 1444 group group NN 1445 1447 of of IN 1448 1451 SLE sle NN 1452 1460 patients patient NNS 1461 1464 who who WP 1465 1474 displayed display VBD 1475 1487 undetectable undetectable JJ 1488 1496 NF-kappa NF-kappa NNP 1497 1498 B B NNP 1499 1507 activity activity NN 1507 1508 , , , 1509 1512 p65 p65 NN 1513 1522 complexes complex NNS 1523 1527 were be VBD 1528 1531 not not RB 1532 1538 formed form VBN 1538 1539 . . . 1540 1547 Finally finally RB 1547 1548 , , , 1549 1559 immunoblot immunoblot NN 1560 1568 analysis analysis NN 1569 1571 of of IN 1572 1579 nuclear nuclear JJ 1580 1588 extracts extract NNS 1589 1595 showed show VBD 1596 1605 decreased decrease VBN 1606 1608 or or CC 1609 1615 absent absent JJ 1616 1619 p65 p65 NN 1620 1627 protein protein NN 1628 1634 levels level NNS 1634 1635 . . . 1636 1638 As as IN 1639 1642 p65 p65 NN 1643 1652 complexes complex NNS 1653 1656 are be VBP 1657 1674 transcriptionally transcriptionally RB 1675 1681 active active JJ 1682 1684 in in IN 1685 1695 comparison comparison NN 1696 1698 to to TO 1699 1702 the the DT 1703 1706 p50 p50 NN 1707 1716 homodimer homodimer NN 1716 1717 , , , 1718 1722 this this DT 1723 1728 novel novel JJ 1729 1736 finding finding NN 1737 1740 may may MD 1741 1748 provide provide VB 1749 1756 insight insight NN 1757 1759 on on IN 1760 1763 the the DT 1764 1770 origin origin NN 1771 1773 of of IN 1774 1782 abnormal abnormal JJ 1783 1791 cytokine cytokine NN 1792 1794 or or CC 1795 1800 other other JJ 1801 1805 gene gene NN 1806 1819 transcription transcription NN 1820 1822 in in IN 1823 1826 SLE sle NN 1827 1835 patients patient NNS 1835 1836 . . .