0 7 Nuclear nuclear JJ 8 31 factor-kappaB-dependent factor-kappab-dependent JJ 32 41 induction induction NN 42 44 of of IN 45 58 interleukin-8 interleukin-8 NN 59 63 gene gene NN 64 74 expression expression NN 75 77 by by IN 78 83 tumor tumor NN 84 92 necrosis necrosis NN 93 99 factor factor NN 100 105 alpha alpha NN 105 106 : : : 107 115 evidence evidence NN 116 119 for for IN 120 122 an an DT 123 134 antioxidant antioxidant JJ 135 144 sensitive sensitive JJ 145 155 activating activate VBG 156 163 pathway pathway NN 164 172 distinct distinct JJ 173 177 from from IN 178 185 nuclear nuclear JJ 186 199 translocation translocation NN 199 200 . . . 202 207 Tumor tumor NN 208 216 necrosis necrosis NN 217 223 factor factor NN 224 229 alpha alpha NN 230 231 ( ( ( 231 239 TNFalpha TNFalpha NNP 239 240 ) ) ) 241 243 is be VBZ 244 245 a a DT 246 257 pluripotent pluripotent JJ 258 267 activator activator NN 268 270 of of IN 271 283 inflammation inflammation NN 284 286 by by IN 287 295 inducing induce VBG 296 297 a a DT 298 313 proinflammatory proinflammatory JJ 314 322 cytokine cytokine NN 323 330 cascade cascade NN 330 331 . . . 332 336 This this DT 337 347 phenomenon phenomenon NN 348 350 is be VBZ 351 359 mediated mediate VBN 359 360 , , , 361 363 in in IN 364 368 part part NN 368 369 , , , 370 377 through through IN 378 387 inducible inducible JJ 388 398 expression expression NN 399 401 of of IN 402 405 the the DT 406 409 CXC CXC NNP 410 419 chemokine chemokine NN 419 420 , , , 421 434 interleukin-8 interleukin-8 NN 435 436 ( ( ( 436 440 IL-8 il-8 NN 440 441 ) ) ) 441 442 . . . 443 445 In in IN 446 450 this this DT 451 456 study study NN 456 457 , , , 458 460 we we PRP 461 472 investigate investigate VBP 473 476 the the DT 477 481 role role NN 482 484 of of IN 485 503 TNFalpha-inducible tnfalpha-inducible JJ 504 512 reactive reactive JJ 513 519 oxygen oxygen NN 520 527 species specie NNS 528 529 ( ( ( 529 532 ROS ROS NNP 532 533 ) ) ) 534 536 in in IN 537 541 IL-8 il-8 NN 542 552 expression expression NN 553 555 by by IN 556 557 “ `` `` 557 570 monocyte-like monocyte-like JJ 570 571 ” '' '' 572 576 U937 u937 NN 577 588 histiocytic histiocytic JJ 589 597 lymphoma lymphoma NN 598 603 cells cell NNS 603 604 . . . 605 613 TNFalpha TNFalpha NNP 614 616 is be VBZ 617 618 a a DT 619 624 rapid rapid JJ 625 634 activator activator NN 635 637 of of IN 638 642 IL-8 il-8 NN 643 647 gene gene NN 648 658 expression expression NN 659 661 by by IN 662 666 U937 u937 NN 666 667 , , , 668 677 producing produce VBG 678 679 a a DT 680 687 50-fold 50-fold JJ 688 697 induction induction NN 698 700 of of IN 701 705 mRNA mRNA NNP 706 712 within within IN 713 714 1 1 CD 715 719 hour hour NN 720 722 of of IN 723 732 treatment treatment NN 732 733 . . . 734 736 In in IN 737 741 gene gene NN 742 754 transfection transfection NN 755 761 assays assay NNS 761 762 , , , 763 766 the the DT 767 773 effect effect NN 774 776 of of IN 777 785 TNFalpha TNFalpha NNP 786 794 requires require VBZ 795 798 the the DT 799 807 presence presence NN 808 810 of of IN 811 813 an an DT 814 823 inducible inducible JJ 824 831 nuclear nuclear JJ 832 845 factor-kappaB factor-kappab NN 846 847 ( ( ( 847 856 NF-kappaB NF-kappaB NNP 856 857 ) ) ) 858 859 ( ( ( 859 862 Rel Rel NNP 863 864 A A NNP 864 865 ) ) ) 866 873 binding binding NN 874 878 site site NN 879 881 in in IN 882 885 the the DT 886 890 IL-8 il-8 NN 891 899 promoter promoter NN 899 900 . . . 901 909 TNFalpha TNFalpha NNP 910 919 treatment treatment NN 920 927 induces induce VBZ 928 929 a a DT 930 935 rapid rapid JJ 936 949 translocation translocation NN 950 952 of of IN 953 956 the the DT 957 959 65 65 CD 960 962 kD kd NN 963 978 transcriptional transcriptional JJ 979 988 activator activator NN 989 998 NF-kappaB nf-kappab NN 999 1006 subunit subunit NN 1006 1007 , , , 1008 1011 Rel Rel NNP 1012 1013 A A NNP 1013 1014 , , , 1015 1020 whose whose WP$ 1021 1028 binding binding NN 1029 1031 in in IN 1032 1035 the the DT 1036 1043 nucleus nucleus NN 1044 1050 occurs occur VBZ 1051 1057 before before IN 1058 1065 changes change NNS 1066 1068 in in IN 1069 1082 intracellular intracellular JJ 1083 1086 ROS ros NN 1086 1087 . . . 1088 1100 Pretreatment Pretreatment NNP 1101 1102 ( ( ( 1102 1104 or or CC 1105 1107 up up IN 1108 1110 to to TO 1111 1113 15 15 CD 1114 1121 minutes minute NNS 1122 1135 posttreatment posttreatment NN 1135 1136 ) ) ) 1137 1145 relative relative JJ 1146 1148 to to TO 1149 1157 TNFalpha TNFalpha NNP 1158 1162 with with IN 1163 1166 the the DT 1167 1178 antioxidant antioxidant JJ 1179 1187 dimethyl dimethyl NN 1188 1197 sulfoxide sulfoxide NN 1198 1199 ( ( ( 1199 1203 DMSO DMSO NNP 1203 1204 ) ) ) 1205 1206 ( ( ( 1206 1207 2 2 CD 1207 1208 % % NN 1209 1210 [ [ ( 1210 1217 vol/vol vol/vol NN 1217 1218 ] ] ) 1218 1219 ) ) ) 1220 1226 blocks block VBZ 1227 1229 80 80 CD 1229 1230 % % NN 1231 1233 of of IN 1234 1253 NF-kappaB-dependent nf-kappab-dependent JJ 1254 1267 transcription transcription NN 1267 1268 . . . 1269 1281 Surprisingly surprisingly RB 1281 1282 , , , 1283 1290 however however RB 1290 1291 , , , 1292 1296 DMSO dmso NN 1297 1300 has have VBZ 1301 1303 no no DT 1304 1310 effect effect NN 1311 1313 on on IN 1314 1323 inducible inducible JJ 1324 1327 Rel Rel NNP 1328 1329 A a NN 1330 1337 binding binding NN 1337 1338 . . . 1339 1346 Similar similar JJ 1347 1356 selective selective JJ 1357 1364 effects effect NNS 1365 1367 on on IN 1368 1377 NF-kappaB NF-kappaB NNP 1378 1391 transcription transcription NN 1392 1395 are be VBP 1396 1400 seen see VBN 1401 1405 with with IN 1406 1409 the the DT 1410 1419 unrelated unrelated JJ 1420 1432 antioxidants antioxidant NNS 1432 1433 , , , 1434 1450 N-acetylcysteine N-acetylcysteine NNP 1451 1452 ( ( ( 1452 1455 NAC NAC NNP 1455 1456 ) ) ) 1457 1460 and and CC 1461 1468 vitamin vitamin NN 1469 1470 C C NNP 1470 1471 . . . 1472 1477 These these DT 1478 1482 data datum NNS 1483 1491 indicate indicate VBP 1492 1496 that that IN 1497 1505 TNFalpha TNFalpha NNP 1506 1513 induces induce VBZ 1514 1515 a a DT 1516 1523 delayed delay VBN 1524 1537 ROS-dependent ros-dependent JJ 1538 1548 signalling signalling NN 1549 1556 pathway pathway NN 1557 1561 that that WDT 1562 1564 is be VBZ 1565 1573 required require VBN 1574 1577 for for IN 1578 1587 NF-kappaB NF-kappaB NNP 1588 1603 transcriptional transcriptional JJ 1604 1614 activation activation NN 1615 1618 and and CC 1619 1621 is be VBZ 1622 1631 separable separable JJ 1632 1636 from from IN 1637 1641 that that DT 1642 1650 required require VBN 1651 1654 for for IN 1655 1658 its its PRP$ 1659 1666 nuclear nuclear JJ 1667 1680 translocation translocation NN 1680 1681 . . . 1682 1689 Further further JJ 1690 1700 definition definition NN 1701 1703 of of IN 1704 1708 this this DT 1709 1716 pathway pathway NN 1717 1721 will will MD 1722 1727 yield yield VB 1728 1731 new new JJ 1732 1740 insights insight NNS 1741 1745 into into IN 1746 1758 inflammation inflammation NN 1759 1768 initiated initiate VBN 1769 1771 by by IN 1772 1780 TNFalpha TNFalpha NNP 1781 1791 signalling signalling NN 1791 1792 . . .