0 4 Role role NN 5 7 of of IN 8 12 IKK1 ikk1 NN 13 16 and and CC 17 21 IKK2 ikk2 NN 22 24 in in IN 25 43 lipopolysaccharide lipopolysaccharide NN 44 53 signaling signaling NN 54 56 in in IN 57 62 human human JJ 63 72 monocytic monocytic JJ 73 78 cells cell NNS 78 79 . . . 81 92 Mononuclear mononuclear JJ 93 103 phagocytes phagocyte NNS 104 108 play play VBP 109 110 a a DT 111 116 major major JJ 117 121 role role NN 122 124 in in IN 125 131 immune immune JJ 132 135 and and CC 136 148 inflammatory inflammatory JJ 149 158 responses response NNS 158 159 . . . 160 169 Bacterial bacterial JJ 170 188 lipopolysaccharide lipopolysaccharide NN 189 190 ( ( ( 190 193 LPS LPS NNP 193 194 ) ) ) 195 202 induces induce VBZ 203 212 monocytes monocyte NNS 213 215 to to TO 216 223 express express VB 224 225 a a DT 226 233 variety variety NN 234 236 of of IN 237 242 genes gene NNS 243 245 by by IN 246 256 activating activate VBG 257 260 the the DT 261 274 NF-kappaB/Rel NF-kappaB/Rel NNP 275 288 transcription transcription NN 289 295 factor factor NN 296 302 family family NN 302 303 . . . 304 312 Recently recently RB 312 313 , , , 314 316 we we PRP 317 321 have have VBP 322 330 reported report VBN 331 335 that that IN 336 339 the the DT 340 345 tumor tumor NN 346 354 necrosis necrosis NN 355 361 factor factor NN 362 365 and and CC 366 377 interleukin interleukin NN 378 379 1 1 CD 380 389 signaling signaling NN 390 398 pathways pathway NNS 399 407 activate activate VBP 408 411 two two CD 412 419 kinases kinase NNS 419 420 , , , 421 425 IKK1 IKK1 NNP 426 429 and and CC 430 434 IKK2 IKK2 NNP 434 435 . . . 436 451 Phosphorylation phosphorylation NN 452 454 of of IN 455 458 the the DT 459 466 IkappaB IkappaB NNP 467 478 cytoplasmic cytoplasmic JJ 479 489 inhibitors inhibitor NNS 489 490 , , , 491 503 IkappaBalpha IkappaBalpha NNP 503 504 , , , 505 516 IkappaBbeta IkappaBbeta NNP 516 517 , , , 518 521 and and CC 522 536 IkappaBepsilon IkappaBepsilon NNP 536 537 , , , 538 540 by by IN 541 546 these these DT 547 554 kinases kinase NNS 555 563 triggers trigger VBZ 564 575 proteolytic proteolytic JJ 576 587 degradation degradation NN 588 591 and and CC 592 595 the the DT 596 603 release release NN 604 606 of of IN 607 620 NF-kappaB/Rel NF-kappaB/Rel NNP 621 629 proteins protein NNS 630 634 into into IN 635 638 the the DT 639 646 nucleus nucleus NN 646 647 . . . 648 650 At at IN 651 658 present present NN 658 659 , , , 660 663 the the DT 664 668 role role NN 669 671 of of IN 672 675 the the DT 676 680 IKKs ikk NNS 681 683 in in IN 684 687 LPS lps NN 688 697 signaling signaling NN 698 701 has have VBZ 702 705 not not RB 706 710 been be VBN 711 723 investigated investigate VBN 723 724 . . . 725 729 Here here RB 729 730 , , , 731 733 we we PRP 734 740 report report VBP 741 745 that that IN 746 749 LPS LPS NNP 750 757 induces induce VBZ 758 761 IKK IKK NNP 762 770 activity activity NN 771 773 in in IN 774 779 human human JJ 780 789 monocytes monocyte NNS 790 793 and and CC 794 799 THP-1 thp-1 NN 800 809 monocytic monocytic JJ 810 815 cells cell NNS 815 816 . . . 817 820 The the DT 821 829 kinetics kinetic NNS 830 832 of of IN 833 843 activation activation NN 844 846 of of IN 847 853 kinase kinase NNP 854 862 activity activity NN 863 865 in in IN 866 875 monocytic monocytic JJ 876 881 cells cell NNS 882 885 are be VBP 886 896 relatively relatively RB 897 901 slow slow JJ 902 906 with with IN 907 914 maximal maximal JJ 915 923 activity activity NN 924 932 observed observe VBN 933 935 at at IN 936 938 60 60 CD 939 942 min min NN 942 943 , , , 944 949 which which WDT 950 959 coincides coincide VBZ 960 964 with with IN 965 968 the the DT 969 980 degradation degradation NN 981 983 of of IN 984 992 IkappaBs IkappaB NNP 993 996 and and CC 997 1000 the the DT 1001 1008 nuclear nuclear JJ 1009 1022 translocation translocation NN 1023 1025 of of IN 1026 1035 NF-kappaB NF-kappaB NNP 1035 1036 . . . 1037 1039 In in IN 1040 1052 transfection transfection NN 1053 1064 experiments experiment NNS 1064 1065 , , , 1066 1080 overexpression overexpression NN 1081 1083 of of IN 1084 1088 wild wild JJ 1089 1093 type type NN 1094 1098 IKK1 ikk1 NN 1098 1099 , , , 1100 1101 a a DT 1102 1110 dominant dominant JJ 1111 1119 negative negative JJ 1120 1126 mutant mutant JJ 1127 1131 IKK1 ikk1 NN 1132 1133 ( ( ( 1133 1137 K44M K44M NNP 1137 1138 ) ) ) 1138 1139 , , , 1140 1142 or or CC 1143 1147 wild wild JJ 1148 1152 type type NN 1153 1157 IKK2 ikk2 NN 1158 1161 did do VBD 1162 1165 not not RB 1166 1172 affect affect VB 1173 1184 LPS-induced lps-induced JJ 1185 1201 kappaB-dependent kappab-dependent JJ 1202 1215 transcription transcription NN 1216 1218 in in IN 1219 1228 monocytic monocytic JJ 1229 1234 cells cell NNS 1234 1235 . . . 1236 1238 In in IN 1239 1247 contrast contrast NN 1247 1248 , , , 1249 1250 a a DT 1251 1259 dominant dominant JJ 1260 1268 negative negative JJ 1269 1275 mutant mutant NN 1276 1278 of of IN 1279 1283 IKK2 IKK2 NNP 1284 1293 inhibited inhibit VBD 1294 1297 LPS LPS NNP 1298 1307 induction induction NN 1308 1310 of of IN 1311 1327 kappaB-dependent kappab-dependent JJ 1328 1341 transcription transcription NN 1342 1344 in in IN 1345 1346 a a DT 1347 1361 dose-dependent dose-dependent JJ 1362 1368 manner manner NN 1368 1369 . . . 1370 1375 These these DT 1376 1383 results result NNS 1384 1392 indicate indicate VBP 1393 1397 that that IN 1398 1401 LPS LPS NNP 1402 1411 induction induction NN 1412 1414 of of IN 1415 1431 kappaB-dependent kappab-dependent JJ 1432 1436 gene gene NN 1437 1447 expression expression NN 1448 1450 in in IN 1451 1456 human human JJ 1457 1466 monocytic monocytic JJ 1467 1472 cells cell NNS 1473 1481 requires require VBZ 1482 1492 activation activation NN 1493 1495 of of IN 1496 1500 IKK2 ikk2 NN 1500 1501 . . .