0 8 Protease Protease NNP 9 19 inhibitors inhibitor NNS 20 25 block block VBP 26 44 lipopolysaccharide lipopolysaccharide NN 45 54 induction induction NN 55 57 of of IN 58 64 tissue tissue NN 65 71 factor factor NN 72 76 gene gene NN 77 87 expression expression NN 88 90 in in IN 91 96 human human JJ 97 106 monocytic monocytic JJ 107 112 cells cell NNS 113 115 by by IN 116 126 preventing prevent VBG 127 137 activation activation NN 138 140 of of IN 141 150 c-Rel/p65 c-rel/p65 NN 151 163 heterodimers heterodimer NNS 163 164 . . . 166 172 Tissue tissue NN 173 179 factor factor NN 180 181 ( ( ( 181 183 TF TF NNP 183 184 ) ) ) 185 187 is be VBZ 188 197 expressed express VBN 198 205 rapidly rapidly RB 206 208 by by IN 209 214 human human JJ 215 224 monocytes monocyte NNS 225 232 exposed expose VBN 233 235 to to TO 236 245 bacterial bacterial JJ 246 255 endotoxin endotoxin NN 256 257 ( ( ( 257 275 lipopolysaccharide lipopolysaccharide NN 275 276 , , , 277 279 or or CC 280 283 LPS lps NN 283 284 ) ) ) 284 285 . . . 286 301 Transcriptional transcriptional JJ 302 312 regulation regulation NN 313 315 is be VBZ 316 324 mediated mediate VBN 325 327 by by IN 328 335 binding binding NN 336 338 of of IN 339 348 c-Rel/p65 c-rel/p65 NN 349 361 heterodimers heterodimer NNS 362 364 to to TO 365 366 a a DT 367 372 kappa kappa NN 373 379 B-like b-like JJ 380 384 site site NN 385 387 in in IN 388 391 the the DT 392 394 TF TF NNP 395 403 promoter promoter NN 403 404 . . . 405 412 Nuclear nuclear JJ 413 426 translocation translocation NN 427 429 of of IN 430 439 cytosolic cytosolic JJ 440 449 c-Rel/p65 c-rel/p65 NN 450 462 heterodimers heterodimer NNS 463 466 and and CC 467 472 other other JJ 473 480 members member NNS 481 483 of of IN 484 487 the the DT 488 496 NF-kappa NF-kappa NNP 497 502 B/Rel B/Rel NNP 503 509 family family NN 510 518 requires require VBZ 519 531 dissociation dissociation NN 532 535 and and CC 536 547 proteolytic proteolytic JJ 548 559 degradation degradation NN 560 562 of of IN 563 566 the the DT 567 576 inhibitor inhibitor NN 577 584 protein protein NN 584 585 , , , 586 587 I i NN 588 593 kappa kappa NN 594 595 B B NNP 596 601 alpha alpha NN 601 602 . . . 603 606 The the DT 607 615 protease protease NN 616 626 inhibitors inhibitor NNS 627 628 N N NNP 629 652 alpha-tosylphenylalanyl alpha-tosylphenylalanyl NN 653 665 chloromethyl chloromethyl NN 666 672 ketone ketone NN 673 674 ( ( ( 674 678 TPCK TPCK NNP 678 679 ) ) ) 680 683 and and CC 684 685 N N NNP 686 706 alpha-tosyl-L-lysine alpha-tosyl-l-lysine NN 707 719 chloromethyl chloromethyl NN 720 726 ketone ketone NN 727 728 ( ( ( 728 732 TLCK TLCK NNP 732 733 ) ) ) 734 739 block block VBP 740 750 activation activation NN 751 753 of of IN 754 762 NF-kappa NF-kappa NNP 763 768 B/Rel B/Rel NNP 769 777 proteins protein NNS 778 780 by by IN 781 791 preventing prevent VBG 792 803 degradation degradation NN 804 806 of of IN 807 808 I i NN 809 814 kappa kappa NN 815 816 B B NNP 817 822 alpha alpha NN 822 823 . . . 824 826 To to TO 827 836 determine determine VB 837 839 if if IN 840 844 TPCK TPCK NNP 845 848 and and CC 849 853 TLCK TLCK NNP 854 863 inhibited inhibit VBD 864 867 LPS LPS NNP 868 877 induction induction NN 878 880 of of IN 881 883 TF TF NNP 884 894 expression expression NN 894 895 , , , 896 903 freshly freshly RB 904 912 isolated isolate VBN 913 918 human human JJ 919 928 monocytes monocyte NNS 929 932 and and CC 933 942 monocytic monocytic JJ 943 948 THP-1 thp-1 NN 949 954 cells cell NNS 955 959 were be VBD 960 970 pretreated pretreate VBN 971 975 with with IN 976 981 these these DT 982 992 inhibitors inhibitor NNS 993 996 for for IN 997 999 30 30 CD 1000 1003 min min NN 1004 1010 before before IN 1011 1014 LPS LPS NNP 1015 1026 stimulation stimulation NN 1026 1027 . . . 1028 1032 Both both CC 1033 1037 TPCK TPCK NNP 1038 1041 and and CC 1042 1046 TLCK TLCK NNP 1047 1056 inhibited inhibit VBD 1057 1060 LPS LPS NNP 1061 1070 induction induction NN 1071 1073 of of IN 1074 1076 TF TF NNP 1077 1084 protein protein NN 1084 1085 , , , 1086 1088 TF TF NNP 1089 1093 mRNA mRNA NNP 1094 1097 and and CC 1098 1100 TF TF NNP 1101 1109 promoter promoter NN 1110 1118 activity activity NN 1119 1121 in in IN 1122 1123 a a DT 1124 1138 dose-dependent dose-dependent JJ 1139 1145 manner manner NN 1145 1146 . . . 1147 1152 These these DT 1153 1163 inhibitors inhibitor NNS 1164 1176 specifically specifically RB 1177 1186 prevented prevent VBD 1187 1198 degradation degradation NN 1199 1201 of of IN 1202 1203 I i NN 1204 1209 kappa kappa NN 1210 1211 B B NNP 1212 1217 alpha alpha NN 1218 1221 and and CC 1222 1229 nuclear nuclear JJ 1230 1243 translocation translocation NN 1244 1246 of of IN 1247 1256 c-Rel/p65 c-rel/p65 NN 1257 1269 heterodimers heterodimer NNS 1269 1270 . . . 1271 1273 In in IN 1274 1282 contrast contrast NN 1282 1283 , , , 1284 1288 TPCK TPCK NNP 1289 1292 and and CC 1293 1297 TLCK TLCK NNP 1298 1301 did do VBD 1302 1305 not not RB 1306 1311 block block VB 1312 1321 induction induction NN 1322 1324 of of IN 1325 1327 an an DT 1328 1343 immediate-early immediate-early JJ 1344 1348 gene gene NN 1349 1357 encoding encode VBG 1358 1361 the the DT 1362 1375 transcription transcription NN 1376 1382 factor factor NN 1382 1383 , , , 1384 1389 Egr-1 Egr-1 NNP 1389 1390 . . . 1391 1396 Taken take VBN 1397 1405 together together RB 1405 1406 , , , 1407 1412 these these DT 1413 1417 data datum NNS 1418 1427 indicated indicate VBD 1428 1432 that that IN 1433 1443 inhibiting inhibit VBG 1444 1451 nuclear nuclear JJ 1452 1465 translocation translocation NN 1466 1468 of of IN 1469 1478 c-Rel/p65 c-rel/p65 NN 1479 1491 heterodimers heterodimer NNS 1492 1501 prevented prevent VBD 1502 1505 LPS LPS NNP 1506 1515 induction induction NN 1516 1518 of of IN 1519 1521 TF TF NNP 1522 1526 gene gene NN 1527 1540 transcription transcription NN 1541 1543 in in IN 1544 1553 monocytic monocytic JJ 1554 1559 cells cell NNS 1559 1560 . . .