0 1 A a DT 2 7 thiol thiol NN 8 19 antioxidant antioxidant NN 20 29 regulates regulate VBZ 30 33 IgE ige NN 34 41 isotype isotype NN 42 51 switching switching NN 52 54 by by IN 55 65 inhibiting inhibit VBG 66 76 activation activation NN 77 79 of of IN 80 87 nuclear nuclear JJ 88 101 factor-kappaB factor-kappab NN 101 102 . . . 104 107 The the DT 108 115 binding bind VBG 116 120 site site NN 121 124 for for IN 125 132 nuclear nuclear JJ 133 146 factor-kappaB factor-kappaB NNP 147 148 ( ( ( 148 157 NF-kappaB NF-kappaB NNP 157 158 ) ) ) 159 161 is be VBZ 162 169 present present JJ 170 172 at at IN 173 176 the the DT 177 185 promoter promoter NN 186 192 region region NN 193 195 of of IN 196 199 the the DT 200 208 germline germline NN 209 217 Cepsilon Cepsilon NNP 218 222 gene gene NN 222 223 , , , 224 227 but but CC 228 233 there there EX 234 236 is be VBZ 237 243 little little JJ 244 255 information information NN 256 258 on on IN 259 266 whether whether IN 267 271 this this DT 272 278 factor factor NN 279 281 is be VBZ 282 290 involved involve VBN 291 293 in in IN 294 304 regulating regulate VBG 305 308 IgE ige NN 309 318 synthesis synthesis NN 319 321 by by IN 322 327 human human JJ 328 329 B B NNP 330 335 cells cell NNS 335 336 . . . 337 348 Accordingly accordingly RB 348 349 , , , 350 352 we we PRP 353 360 studied study VBD 361 364 the the DT 365 369 role role NN 370 372 of of IN 373 382 NF-kappaB NF-kappaB NNP 383 385 in in IN 386 394 germline germline NN 395 403 Cepsilon Cepsilon NNP 404 417 transcription transcription NN 418 420 by by IN 421 426 using use VBG 427 430 two two CD 431 436 human human JJ 437 444 Burkitt Burkitt NNP 444 446 ’s 's POS 447 455 lymphoma lymphoma NN 456 457 B B NNP 458 462 cell cell NN 463 468 lines line NNS 468 469 , , , 470 475 DND39 DND39 NNP 476 479 and and CC 480 484 DG75 DG75 NNP 484 485 . . . 486 488 In in IN 489 493 both both DT 494 498 cell cell NN 499 504 lines line NNS 504 505 , , , 506 525 n-acetyl-L-cysteine n-acetyl-l-cysteine NN 526 527 ( ( ( 527 530 NAC NAC NNP 530 531 ) ) ) 531 532 , , , 533 534 a a DT 535 541 potent potent JJ 542 547 thiol thiol NN 548 559 antioxidant antioxidant NN 559 560 , , , 561 570 inhibited inhibit VBD 571 574 the the DT 575 585 triggering triggering NN 586 588 of of IN 589 592 the the DT 593 600 nuclear nuclear JJ 601 611 expression expression NN 612 614 of of IN 615 624 NF-kappaB NF-kappaB NNP 625 627 by by IN 628 632 IL-4 il-4 NN 633 636 and and CC 637 639 by by IN 640 649 anti-CD40 anti-cd40 JJ 650 660 monoclonal monoclonal JJ 661 669 antibody antibody NN 669 670 . . . 671 679 Although although IN 680 684 IL-4 il-4 NN 685 694 activated activate VBD 695 701 signal signal NN 702 713 transducers transducer NNS 714 717 and and CC 718 728 activators activator NNS 729 731 of of IN 732 745 transcription transcription NN 746 747 ( ( ( 747 751 STAT STAT NNP 751 752 ) ) ) 753 754 6 6 CD 755 757 in in IN 758 766 addition addition NN 767 769 to to TO 770 779 NF-kappaB NF-kappaB NNP 779 780 , , , 781 784 NAC NAC NNP 785 794 treatment treatment NN 795 797 or or CC 798 801 the the DT 802 814 transfection transfection NN 815 817 of of IN 818 823 decoy decoy NN 824 845 oligodeoxynucleotides oligodeoxynucleotide NNS 846 849 for for IN 850 859 NF-kappaB NF-kappaB NNP 860 862 or or CC 863 868 STAT6 STAT6 NNP 869 873 only only RB 874 880 partly partly RB 881 888 blocked block VBD 889 901 IL-4-induced il-4-induced JJ 902 910 germline germline NN 911 919 Cepsilon Cepsilon NNP 920 933 transcription transcription NN 933 934 . . . 935 942 However however RB 942 943 , , , 944 949 these these DT 950 953 two two CD 954 959 decoy decoy NN 960 981 oligodeoxynucleotides oligodeoxynucleotide NNS 982 990 together together RB 991 997 almost almost RB 998 1008 completely completely RB 1009 1018 abrogated abrogate VBD 1019 1031 IL-4-induced il-4-induced JJ 1032 1040 germline germline NN 1041 1049 Cepsilon Cepsilon NNP 1050 1063 transcription transcription NN 1063 1064 . . . 1065 1067 Of of IN 1068 1072 note note NN 1072 1073 , , , 1074 1087 CD40-mediated cd40-mediated JJ 1088 1099 enhancement enhancement NN 1100 1102 of of IN 1103 1114 IL-4-driven il-4-driven JJ 1115 1123 germline germline NN 1124 1132 Cepsilon Cepsilon NNP 1133 1146 transcription transcription NN 1147 1150 was be VBD 1151 1159 markedly markedly RB 1160 1169 decreased decrease VBN 1170 1172 by by IN 1173 1176 NAC NAC NNP 1177 1179 or or CC 1180 1182 by by IN 1183 1184 a a DT 1185 1190 decoy decoy NN 1191 1211 oligodeoxynucleotide oligodeoxynucleotide NN 1212 1215 for for IN 1216 1225 NF-kappaB NF-kappaB NNP 1225 1226 . . . 1227 1230 The the DT 1231 1237 effect effect NN 1238 1240 of of IN 1241 1244 NAC NAC NNP 1245 1248 was be VBD 1249 1253 also also RB 1254 1262 examined examine VBN 1263 1265 on on IN 1266 1276 deletional deletional JJ 1277 1283 switch switch NN 1284 1297 recombination recombination NN 1298 1308 underlying underlie VBG 1309 1312 the the DT 1313 1320 isotype isotype NN 1321 1327 switch switch NN 1328 1330 to to TO 1331 1334 IgE ige NN 1334 1335 . . . 1336 1339 NAC NAC NNP 1340 1349 inhibited inhibit VBD 1350 1353 the the DT 1354 1364 generation generation NN 1365 1367 of of IN 1368 1380 Smu/Sepsilon Smu/Sepsilon NNP 1381 1387 switch switch NN 1388 1397 fragments fragment NNS 1398 1400 in in IN 1401 1407 normal normal JJ 1408 1413 human human JJ 1414 1415 B b NN 1416 1421 cells cell NNS 1422 1434 costimulated costimulate VBN 1435 1439 with with IN 1440 1444 IL-4 il-4 NN 1445 1448 and and CC 1449 1458 anti-CD40 anti-cd40 JJ 1459 1469 monoclonal monoclonal JJ 1470 1478 antibody antibody NN 1478 1479 . . . 1480 1482 It it PRP 1483 1487 also also RB 1488 1497 abolished abolish VBD 1498 1510 IL-4-induced il-4-induced JJ 1511 1523 upregulation upregulation NN 1524 1526 of of IN 1527 1531 CD40 CD40 NNP 1532 1535 but but CC 1536 1544 promoted promote VBD 1545 1557 upregulation upregulation NN 1558 1560 of of IN 1561 1565 CD23 CD23 NNP 1565 1566 . . . 1567 1572 These these DT 1573 1580 results result NNS 1581 1588 suggest suggest VBP 1589 1593 that that IN 1594 1606 coordination coordination NN 1607 1609 of of IN 1610 1619 NF-kappaB NF-kappaB NNP 1620 1623 and and CC 1624 1629 STAT6 STAT6 NNP 1630 1633 may may MD 1634 1636 be be VB 1637 1645 required require VBN 1646 1649 for for IN 1650 1659 induction induction NN 1660 1662 of of IN 1663 1671 germline germline NN 1672 1680 Cepsilon Cepsilon NNP 1681 1694 transcription transcription NN 1695 1697 by by IN 1698 1702 IL-4 il-4 NN 1702 1703 , , , 1704 1707 and and CC 1708 1712 that that IN 1713 1726 CD40-mediated cd40-mediated JJ 1727 1736 NF-kappaB NF-kappaB NNP 1737 1747 activation activation NN 1748 1751 may may MD 1752 1754 be be VB 1755 1764 important important JJ 1765 1767 in in IN 1768 1778 regulating regulate VBG 1779 1783 both both CC 1784 1795 enhancement enhancement NN 1796 1798 of of IN 1799 1807 germline germline NN 1808 1816 Cepsilon Cepsilon NNP 1817 1830 transcription transcription NN 1831 1834 and and CC 1835 1840 class class NN 1841 1850 switching switching NN 1851 1853 to to TO 1854 1857 IgE IgE NNP 1857 1858 . . .