0 9 IFN-gamma IFN-gamma NNP 10 17 priming priming NN 18 20 of of IN 21 30 monocytes monocyte NNS 31 39 enhances enhance VBZ 40 51 LPS-induced lps-induced JJ 52 55 TNF tnf NN 56 66 production production NN 67 69 by by IN 70 80 augmenting augment VBG 81 85 both both CC 86 99 transcription transcription NN 100 103 and and CC 104 108 MRNA MRNA NNP 109 118 stability stability NN 118 119 . . . 121 124 The the DT 125 134 induction induction NN 135 137 of of IN 138 146 cytokine cytokine NN 147 157 expression expression NN 158 160 in in IN 161 182 monocytes/macrophages monocytes/macrophage NNS 183 185 by by IN 186 195 bacterial bacterial JJ 196 205 endotoxin endotoxin NN 206 208 or or CC 209 227 lipopolysaccharide lipopolysaccharide NN 228 230 is be VBZ 231 232 a a DT 233 241 critical critical JJ 241 242 , , , 243 249 highly highly RB 250 259 regulated regulate VBN 260 264 host host NN 265 272 defence defence NN 273 281 response response NN 281 282 . . . 283 286 The the DT 287 299 augmentation augmentation NN 300 302 of of IN 303 306 LPS LPS NNP 307 316 responses response NNS 317 319 by by IN 320 330 interferon interferon NN 331 336 gamma gamma NN 337 338 ( ( ( 338 347 IFN-gamma IFN-gamma NNP 347 348 ) ) ) 348 349 , , , 350 358 referred refer VBN 359 361 to to TO 362 364 as as IN 365 372 priming priming NN 372 373 , , , 374 376 is be VBZ 377 381 well well RB 382 393 established establish VBN 393 394 . . . 395 402 However however RB 402 403 , , , 404 407 the the DT 408 420 mechanism(s) mechanism(s) NN 421 423 by by IN 424 429 which which WDT 430 437 priming priming NN 438 444 occurs occur VBZ 445 447 is be VBZ 448 454 poorly poorly RB 455 462 defined define VBN 462 463 . . . 464 469 Using use VBG 470 476 tumour tumour NN 477 485 necrosis necrosis NN 486 492 factor factor NN 493 494 ( ( ( 494 497 TNF TNF NNP 497 498 ) ) ) 499 508 induction induction NN 509 511 as as IN 512 513 a a DT 514 519 model model NN 519 520 , , , 521 532 experiments experiment NNS 533 537 were be VBD 538 546 designed design VBN 547 549 to to TO 550 557 analyse analyse VB 558 560 in in IN 561 567 detail detail NN 568 571 the the DT 572 579 priming priming NN 580 586 effect effect NN 587 589 on on IN 590 593 the the DT 594 597 LPS LPS NNP 598 606 response response NN 607 609 in in IN 610 615 human human JJ 616 625 monocytes monocyte NNS 625 626 . . . 627 634 Priming Priming NNP 635 637 by by IN 638 647 IFN-gamma IFN-gamma NNP 648 651 was be VBD 652 661 primarily primarily RB 662 672 manifested manifest VBN 673 675 at at IN 676 679 the the DT 680 685 level level NN 686 688 of of IN 689 692 TNF TNF NNP 693 697 mRNA mRNA NNP 698 710 accumulation accumulation NN 710 711 . . . 712 721 IFN-gamma IFN-gamma NNP 722 735 pre-treatment pre-treatment NN 736 744 affected affect VBD 745 748 the the DT 749 758 magnitude magnitude NN 759 765 rather rather RB 766 770 than than IN 771 774 the the DT 775 786 sensitivity sensitivity NN 787 789 of of IN 790 793 the the DT 794 797 LPS LPS NNP 798 806 response response NN 806 807 . . . 808 815 Priming Priming NNP 816 824 occurred occur VBD 825 830 after after IN 831 838 several several JJ 839 844 hours hour NNS 845 847 of of IN 848 857 treatment treatment NN 857 858 , , , 859 862 and and CC 863 866 the the DT 867 873 primed prim VBN 874 879 state state NN 880 883 was be VBD 884 891 induced induce VBN 892 894 by by IN 895 901 either either CC 902 911 IFN-gamma IFN-gamma NNP 912 914 or or CC 915 921 GM-CSF GM-CSF NNP 921 922 , , , 923 926 but but CC 927 930 not not RB 931 936 M-CSF M-CSF NNP 936 937 . . . 938 944 Primed prim VBN 945 954 monocytes monocyte NNS 955 966 transcribed transcribe VBD 967 970 TNF TNF NNP 971 975 mRNA mRNA NNP 976 978 at at IN 979 980 a a DT 981 987 higher high JJR 988 992 rate rate NN 993 997 than than IN 998 1005 freshly freshly RB 1006 1014 isolated isolate VBN 1015 1024 monocytes monocyte NNS 1025 1029 upon upon IN 1030 1040 activation activation NN 1041 1045 with with IN 1046 1049 LPS LPS NNP 1049 1050 . . . 1051 1054 The the DT 1055 1064 increased increase VBN 1065 1080 transcriptional transcriptional JJ 1081 1085 rate rate NN 1086 1096 correlated correlate VBD 1097 1101 with with IN 1102 1103 a a DT 1104 1110 marked marked JJ 1111 1119 increase increase NN 1120 1122 in in IN 1123 1130 nuclear nuclear JJ 1131 1143 factor-kappa factor-kappa NN 1144 1145 B B NNP 1146 1154 activity activity NN 1155 1157 in in IN 1158 1163 these these DT 1164 1169 cells cell NNS 1170 1172 as as IN 1173 1183 determined determine VBN 1184 1186 by by IN 1187 1202 electrophoretic electrophoretic JJ 1203 1211 mobility mobility NN 1212 1217 shift shift NN 1218 1223 assay assay NN 1224 1229 using use VBG 1230 1231 a a DT 1232 1241 consensus consensus NN 1242 1250 NF-kappa NF-kappa NNP 1251 1252 B B NNP 1253 1268 oligonucleotide oligonucleotide NN 1268 1269 . . . 1270 1272 An an DT 1273 1283 additional additional JJ 1284 1295 significant significant JJ 1296 1303 finding finding NN 1304 1307 was be VBD 1308 1312 than than IN 1313 1316 TNF TNF NNP 1317 1321 mRNA mRNA NNP 1322 1329 induced induce VBN 1330 1332 in in IN 1333 1339 primed prim VBN 1340 1345 cells cell NNS 1346 1349 was be VBD 1350 1354 much much RB 1355 1359 more more RBR 1360 1366 stable stable JJ 1367 1371 than than IN 1372 1374 in in IN 1375 1383 unprimed unprimed JJ 1384 1389 cells cell NNS 1390 1391 ( ( ( 1391 1395 T1/2 T1/2 NNP 1396 1405 increased increase VBD 1406 1414 6-8-fold 6-8-fold RB 1414 1415 ) ) ) 1415 1416 . . . 1417 1427 Consistent consistent JJ 1428 1432 with with IN 1433 1436 the the DT 1437 1446 increased increase VBN 1447 1451 mRNA mrna NN 1452 1461 stability stability NN 1461 1462 , , , 1463 1466 the the DT 1467 1475 duration duration NN 1476 1478 of of IN 1479 1483 mRNA mrna NN 1484 1496 accumulation accumulation NN 1497 1500 was be VBD 1501 1507 longer longer RBR 1508 1517 following follow VBG 1518 1521 LPS LPS NNP 1522 1533 stimulation stimulation NN 1534 1536 in in IN 1537 1543 primed prim VBN 1544 1553 monocytes monocyte NNS 1553 1554 , , , 1555 1557 in in IN 1558 1566 addition addition NN 1567 1569 to to TO 1570 1575 being be VBG 1576 1578 of of IN 1579 1586 greater great JJR 1587 1596 magnitude magnitude NN 1596 1597 . . . 1598 1605 Finally finally RB 1605 1606 , , , 1607 1613 primed prim VBN 1614 1617 and and CC 1618 1626 unprimed unprimed JJ 1627 1632 cells cell NNS 1633 1642 possessed possess VBD 1643 1644 a a DT 1645 1657 differential differential JJ 1658 1669 sensitivity sensitivity NN 1670 1672 to to TO 1673 1676 the the DT 1677 1683 kinase kinase NNP 1684 1693 inhibitor inhibitor NN 1694 1698 H-89 h-89 NN 1698 1699 . . . 1700 1704 H-89 H-89 NNP 1705 1718 substantially substantially RB 1719 1729 suppressed suppress VBD 1730 1741 LPS-induced lps-induced JJ 1742 1745 TNF TNF NNP 1746 1750 mRNA mrna NN 1751 1763 accumulation accumulation NN 1764 1766 in in IN 1767 1775 unprimed unprimed JJ 1776 1781 cells cell NNS 1781 1782 , , , 1783 1786 but but CC 1787 1790 had have VBD 1791 1793 no no DT 1794 1800 effect effect NN 1801 1803 on on IN 1804 1810 primed prim VBN 1811 1820 monocytes monocyte NNS 1821 1830 following follow VBG 1831 1834 LPS LPS NNP 1835 1846 stimulation stimulation NN 1846 1847 . . . 1848 1849 ( ( ( 1849 1857 ABSTRACT abstract NN 1858 1867 TRUNCATED truncated VBN 1868 1870 AT at IN 1871 1874 250 250 CD 1875 1880 WORDS words NNS 1880 1881 ) ) )