0 3 The the DT 4 8 role role NN 9 11 of of IN 12 19 nuclear nuclear JJ 20 32 factor-kappa factor-kappa NN 33 34 B b NN 35 37 in in IN 38 46 cytokine cytokine NN 47 51 gene gene NN 52 62 regulation regulation NN 62 63 . . . 65 78 Transcription Transcription NNP 79 86 factors factor NNS 87 90 are be VBP 91 102 DNA-binding dna-binding JJ 103 111 proteins protein NNS 112 116 that that WDT 117 125 regulate regulate VBP 126 130 gene gene NN 131 141 expression expression NN 141 142 . . . 143 150 Nuclear nuclear JJ 151 163 factor-kappa factor-kappa NN 164 165 B B NNP 166 167 ( ( ( 167 175 NF-kappa NF-kappa NNP 176 177 B B NNP 177 178 ) ) ) 179 181 is be VBZ 182 183 a a DT 184 192 critical critical JJ 193 206 transcription transcription NN 207 213 factor factor NN 214 217 for for IN 218 225 maximal maximal JJ 226 236 expression expression NN 237 239 of of IN 240 244 many many JJ 245 254 cytokines cytokine NNS 255 259 that that WDT 260 263 are be VBP 264 272 involved involve VBN 273 275 in in IN 276 279 the the DT 280 292 pathogenesis pathogenesis NN 293 295 of of IN 296 308 inflammatory inflammatory JJ 309 317 diseases disease NNS 317 318 , , , 319 323 such such JJ 324 326 as as IN 327 332 adult adult JJ 333 344 respiratory respiratory JJ 345 353 distress distress NN 354 362 syndrome syndrome NN 363 364 ( ( ( 364 368 ARDS ARDS NNPS 368 369 ) ) ) 370 373 and and CC 374 380 sepsis sepsis NN 381 389 syndrome syndrome NN 389 390 . . . 391 401 Activation Activation NNP 402 405 and and CC 406 416 regulation regulation NN 417 419 of of IN 420 428 NF-kappa NF-kappa NNP 429 430 B B NNP 431 434 are be VBP 435 442 tightly tightly RB 443 453 controlled control VBN 454 456 by by IN 457 458 a a DT 459 464 group group NN 465 467 of of IN 468 478 inhibitory inhibitory JJ 479 487 proteins protein NNS 488 489 ( ( ( 489 490 I i NN 491 496 kappa kappa NN 497 498 B B NNP 498 499 ) ) ) 500 504 that that WDT 505 514 sequester sequester VBP 515 523 NF-kappa NF-kappa NNP 524 525 B B NNP 526 528 in in IN 529 532 the the DT 533 542 cytoplasm cytoplasm NN 543 545 of of IN 546 565 immune/inflammatory immune/inflammatory JJ 566 574 effector effector NN 575 580 cells cell NNS 580 581 . . . 582 590 NF-kappa NF-kappa NNP 591 592 B B NNP 593 603 activation activation NN 604 612 involves involve VBZ 613 621 signaled signal VBN 622 637 phosphorylation phosphorylation NN 637 638 , , , 639 653 ubiquitination ubiquitination NN 653 654 , , , 655 658 and and CC 659 670 proteolysis proteolysis NN 671 673 of of IN 674 675 I i NN 676 681 kappa kappa NN 682 684 B. B. NNP 685 694 Liberated liberate VBD 695 703 NF-kappa NF-kappa NNP 704 705 B B NNP 706 714 migrates migrate NNS 715 717 to to TO 718 721 the the DT 722 729 nucleus nucleus NN 729 730 , , , 731 736 where where WRB 737 739 it it PRP 740 745 binds bind VBZ 746 748 to to TO 749 757 specific specific JJ 758 766 promoter promoter NN 767 772 sites site NNS 773 776 and and CC 777 786 activates activate VBZ 787 791 gene gene NN 792 805 transcription transcription NN 805 806 . . . 807 810 The the DT 811 821 activation activation NN 822 824 of of IN 825 833 NF-kappa NF-kappa NNP 834 835 B B NNP 836 845 initiates initiate VBZ 846 850 both both CC 851 864 extracellular extracellular JJ 865 868 and and CC 869 882 intracellular intracellular JJ 883 893 regulatory regulatory JJ 894 900 events event NNS 901 905 that that WDT 906 912 result result VBP 913 915 in in IN 916 930 autoregulation autoregulation NN 931 933 of of IN 934 937 the the DT 938 950 inflammatory inflammatory JJ 951 958 cascade cascade NN 959 966 through through IN 967 977 modulation modulation NN 978 980 of of IN 981 989 NF-kappa NF-kappa NNP 990 991 B B NNP 992 1002 activation activation NN 1002 1003 . . . 1004 1012 Recently recently RB 1012 1013 , , , 1014 1024 activation activation NN 1025 1027 of of IN 1028 1036 NF-kappa NF-kappa NNP 1037 1038 B B NNP 1039 1042 has have VBZ 1043 1047 been be VBN 1048 1054 linked link VBN 1055 1057 to to TO 1058 1062 ARDS ARDS NNPS 1063 1066 and and CC 1067 1070 has have VBZ 1071 1075 been be VBN 1076 1081 shown show VBN 1082 1084 to to TO 1085 1087 be be VB 1088 1089 a a DT 1090 1098 critical critical JJ 1099 1107 proximal proximal JJ 1108 1112 step step NN 1113 1115 in in IN 1116 1119 the the DT 1120 1130 initiation initiation NN 1131 1133 of of IN 1134 1146 neutrophilic neutrophilic JJ 1147 1159 inflammation inflammation NN 1160 1162 in in IN 1163 1169 animal animal NN 1170 1176 models model NNS 1176 1177 . . . 1178 1188 Activation Activation NNP 1189 1191 of of IN 1192 1200 NF-kappa NF-kappa NNP 1201 1202 B B NNP 1203 1206 can can MD 1207 1209 be be VB 1210 1219 inhibited inhibit VBN 1220 1222 in in FW 1223 1227 vivo vivo FW 1228 1230 by by IN 1231 1240 treatment treatment NN 1241 1245 with with IN 1246 1258 antioxidants antioxidant NNS 1258 1259 , , , 1260 1275 corticosteroids corticosteroid NNS 1275 1276 , , , 1277 1280 and and CC 1281 1284 the the DT 1285 1294 induction induction NN 1295 1297 of of IN 1298 1307 endotoxin endotoxin NN 1308 1317 tolerance tolerance NN 1317 1318 . . . 1319 1333 Identification identification NN 1334 1336 of of IN 1337 1341 more more RBR 1342 1350 specific specific JJ 1351 1354 and and CC 1355 1366 efficacious efficacious JJ 1367 1377 inhibitors inhibitor NNS 1378 1380 of of IN 1381 1389 NF-kappa NF-kappa NNP 1390 1391 B B NNP 1392 1402 activation activation NN 1403 1408 might might MD 1409 1414 prove prove VB 1415 1425 beneficial beneficial JJ 1426 1429 for for IN 1430 1433 the the DT 1434 1443 treatment treatment NN 1444 1446 of of IN 1447 1464 cytokine-mediated cytokine-mediated JJ 1465 1477 inflammatory inflammatory JJ 1478 1486 diseases disease NNS 1486 1487 . . .