0 9 Bacterial bacterial JJ 10 28 lipopolysaccharide lipopolysaccharide NN 29 38 activates activate VBZ 39 46 nuclear nuclear JJ 47 60 factor-kappaB factor-kappab NN 61 68 through through IN 69 82 interleukin-1 interleukin-1 NN 83 92 signaling signaling NN 93 102 mediators mediator NNS 103 105 in in IN 106 114 cultured culture VBN 115 120 human human JJ 121 127 dermal dermal JJ 128 139 endothelial endothelial JJ 140 145 cells cell NNS 146 149 and and CC 150 161 mononuclear mononuclear JJ 162 172 phagocytes phagocyte NNS 172 173 . . . 175 184 Bacterial bacterial JJ 185 203 lipopolysaccharide lipopolysaccharide NN 204 205 ( ( ( 205 218 LPS)-mediated lps)-mediated JJ 219 225 immune immune JJ 226 235 responses response NNS 235 236 , , , 237 246 including include VBG 247 257 activation activation NN 258 260 of of IN 261 270 monocytes monocyte NNS 270 271 , , , 272 283 macrophages macrophage NNS 283 284 , , , 285 288 and and CC 289 300 endothelial endothelial JJ 301 306 cells cell NNS 306 307 , , , 308 312 play play VBP 313 315 an an DT 316 325 important important JJ 326 330 role role NN 331 333 in in IN 334 337 the the DT 338 350 pathogenesis pathogenesis NN 351 353 of of IN 354 367 Gram-negative gram-negative JJ 368 384 bacteria-induced bacteria-induced JJ 385 391 sepsis sepsis NN 392 400 syndrome syndrome NN 400 401 . . . 402 412 Activation Activation NNP 413 415 of of IN 416 425 NF-kappaB NF-kappaB NNP 426 428 is be VBZ 429 436 thought think VBN 437 439 to to TO 440 442 be be VB 443 451 required require VBN 452 455 for for IN 456 464 cytokine cytokine NN 465 472 release release NN 473 477 from from IN 478 492 LPS-responsive lps-responsive JJ 493 498 cells cell NNS 498 499 , , , 500 501 a a DT 502 510 critical critical JJ 511 515 step step NN 516 519 for for IN 520 529 endotoxic endotoxic JJ 530 537 effects effect NNS 537 538 . . . 539 543 Here here RB 544 546 we we PRP 547 559 investigated investigate VBD 560 563 the the DT 564 568 role role NN 569 572 and and CC 573 584 involvement involvement NN 585 587 of of IN 588 601 interleukin-1 interleukin-1 NN 602 603 ( ( ( 603 607 IL-1 il-1 NN 607 608 ) ) ) 609 612 and and CC 613 618 tumor tumor NN 619 627 necrosis necrosis NN 628 634 factor factor NN 635 636 ( ( ( 636 645 TNF-alpha TNF-alpha NNP 645 646 ) ) ) 647 653 signal signal NN 654 664 transducer transducer NN 665 674 molecules molecule NNS 675 677 in in IN 678 681 LPS lps NN 682 691 signaling signaling NN 692 694 in in IN 695 700 human human JJ 701 707 dermal dermal JJ 708 719 microvessel microvessel NN 720 731 endothelial endothelial JJ 732 737 cells cell NNS 738 739 ( ( ( 739 744 HDMEC HDMEC NNP 744 745 ) ) ) 746 749 and and CC 750 755 THP-1 thp-1 NN 756 765 monocytic monocytic JJ 766 771 cells cell NNS 771 772 . . . 773 776 LPS LPS NNP 777 788 stimulation stimulation NN 789 791 of of IN 792 797 HDMEC HDMEC NNP 798 801 and and CC 802 807 THP-1 thp-1 NN 808 813 cells cell NNS 814 823 initiated initiate VBD 824 826 an an DT 827 831 IL-1 il-1 NN 832 845 receptor-like receptor-like JJ 846 855 NF-kappaB nf-kappab NN 856 865 signaling signaling NN 866 873 cascade cascade NN 873 874 . . . 875 877 In in IN 878 887 transient transient JJ 888 902 cotransfection cotransfection NN 903 914 experiments experiment NNS 914 915 , , , 916 924 dominant dominant JJ 925 933 negative negative JJ 934 941 mutants mutant NNS 942 944 of of IN 945 948 the the DT 949 953 IL-1 il-1 NN 954 963 signaling signaling NN 964 971 pathway pathway NN 971 972 , , , 973 982 including include VBG 983 988 MyD88 myd88 NN 988 989 , , , 990 994 IRAK IRAK NNP 994 995 , , , 996 1001 IRAK2 IRAK2 NNP 1001 1002 , , , 1003 1006 and and CC 1007 1012 TRAF6 TRAF6 NNP 1013 1022 inhibited inhibit VBD 1023 1027 both both CC 1028 1033 IL-1- IL-1- NNP 1034 1037 and and CC 1038 1049 LPS-induced lps-induced JJ 1050 1070 NF-kappaB-luciferase NF-kappaB-luciferase NNP 1071 1079 activity activity NN 1079 1080 . . . 1081 1092 LPS-induced lps-induced JJ 1093 1102 NF-kappaB NF-kappaB NNP 1103 1113 activation activation NN 1114 1117 was be VBD 1118 1121 not not RB 1122 1131 inhibited inhibit VBN 1132 1134 by by IN 1135 1136 a a DT 1137 1145 dominant dominant JJ 1146 1154 negative negative JJ 1155 1161 mutant mutant NN 1162 1164 of of IN 1165 1170 TRAF2 TRAF2 NNP 1171 1175 that that WDT 1176 1178 is be VBZ 1179 1187 involved involve VBN 1188 1190 in in IN 1191 1194 TNF TNF NNP 1195 1204 signaling signaling NN 1204 1205 . . . 1206 1217 LPS-induced lps-induced JJ 1218 1228 activation activation NN 1229 1231 of of IN 1232 1252 NF-kappaB-responsive nf-kappab-responsive JJ 1253 1261 reporter reporter NN 1262 1266 gene gene NN 1267 1270 was be VBD 1271 1274 not not RB 1275 1284 inhibited inhibit VBN 1285 1287 by by IN 1288 1292 IL-1 il-1 NN 1293 1301 receptor receptor NN 1302 1312 antagonist antagonist NN 1312 1313 . . . 1314 1318 TLR2 TLR2 NNP 1319 1322 and and CC 1323 1327 TLR4 TLR4 NNP 1328 1332 were be VBD 1333 1342 expressed express VBN 1343 1345 on on IN 1346 1349 the the DT 1350 1354 cell cell NN 1355 1362 surface surface NN 1363 1365 of of IN 1366 1371 HDMEC HDMEC NNP 1372 1375 and and CC 1376 1381 THP-1 thp-1 NN 1382 1387 cells cell NNS 1387 1388 . . . 1389 1394 These these DT 1395 1403 findings finding NNS 1404 1411 suggest suggest VBP 1412 1416 that that IN 1417 1418 a a DT 1419 1425 signal signal NN 1426 1438 transduction transduction NN 1439 1447 molecule molecule NN 1448 1450 in in IN 1451 1454 the the DT 1455 1458 LPS LPS NNP 1459 1467 receptor receptor NN 1468 1475 complex complex NN 1476 1479 may may MD 1480 1486 belong belong VB 1487 1489 to to TO 1490 1493 the the DT 1494 1498 IL-1 il-1 NN 1499 1517 receptor/toll-like receptor/toll-like JJ 1518 1526 receptor receptor NN 1527 1528 ( ( ( 1528 1531 TLR TLR NNP 1531 1532 ) ) ) 1533 1538 super super NN 1539 1545 family family NN 1545 1546 , , , 1547 1550 and and CC 1551 1554 the the DT 1555 1558 LPS lps NN 1559 1568 signaling signaling NN 1569 1576 cascade cascade NN 1577 1581 uses use VBZ 1582 1584 an an DT 1585 1594 analogous analogous JJ 1595 1604 molecular molecular JJ 1605 1614 framework framework NN 1615 1618 for for IN 1619 1628 signaling signaling NN 1629 1631 as as IN 1632 1636 IL-1 il-1 NN 1637 1639 in in IN 1640 1651 mononuclear mononuclear JJ 1652 1662 phagocytes phagocyte NNS 1663 1666 and and CC 1667 1678 endothelial endothelial JJ 1679 1684 cells cell NNS 1684 1685 . . .