0 12 Constitutive constitutive JJ 13 20 nuclear nuclear JJ 21 29 NF-kappa NF-kappa NNP 30 31 B B NNP 32 34 in in IN 35 40 cells cell NNS 41 43 of of IN 44 47 the the DT 48 56 monocyte monocyte NN 57 64 lineage lineage NN 64 65 . . . 67 69 In in IN 70 79 monocytes monocyte NNS 79 80 , , , 81 84 the the DT 85 92 nuclear nuclear JJ 93 99 factor factor NN 100 108 NF-kappa NF-kappa NNP 109 110 B B NNP 111 114 has have VBZ 115 119 been be VBN 120 127 invoked invoke VBN 128 130 as as IN 131 133 an an DT 134 143 important important JJ 144 157 transcription transcription NN 158 164 factor factor NN 165 167 in in IN 168 171 the the DT 172 182 expression expression NN 183 185 of of IN 186 194 cytokine cytokine NN 195 200 genes gene NNS 200 201 , , , 202 204 of of IN 205 217 cell-surface cell-surface JJ 218 227 receptors receptor NNS 228 231 and and CC 232 234 in in IN 235 238 the the DT 239 249 expression expression NN 250 252 of of IN 253 258 human human JJ 259 275 immunodeficiency immunodeficiency NN 276 281 virus virus NN 281 282 . . . 283 285 In in IN 286 290 such such JJ 291 296 cells cell NNS 296 297 , , , 298 301 DNA DNA NNP 302 309 binding binding NN 310 318 activity activity NN 319 321 of of IN 322 330 NF-kappa NF-kappa NNP 331 332 B B NNP 333 336 can can MD 337 339 be be VB 340 348 detected detect VBN 349 356 without without IN 357 368 intentional intentional JJ 369 380 stimulation stimulation NN 380 381 . . . 382 384 In in IN 385 388 our our PRP$ 389 396 studies study NNS 396 397 , , , 398 403 cells cell NNS 404 406 of of IN 407 410 the the DT 411 416 human human JJ 417 426 monocytic monocytic JJ 427 431 line line NN 432 436 Mono Mono NNP 437 440 Mac Mac NNP 441 442 6 6 CD 442 443 , , , 444 452 cultured culture VBN 453 455 in in IN 456 462 medium medium NN 463 473 containing contain VBG 474 484 fetal-calf fetal-calf JJ 485 490 serum serum NN 491 494 and and CC 495 498 low low JJ 499 505 levels level NNS 506 508 of of IN 509 527 lipopolysaccharide lipopolysaccharide NN 528 529 ( ( ( 529 532 LPS LPS NNP 532 533 ) ) ) 533 534 , , , 535 539 also also RB 540 547 exhibit exhibit VBP 548 552 such such JJ 553 554 ‘ ` `` 554 566 constitutive constitutive JJ 566 567 ’ ' '' 568 576 NF-kappa NF-kappa NNP 577 578 B B NNP 578 579 , , , 580 582 as as IN 583 595 demonstrated demonstrate VBN 596 598 by by IN 599 613 mobility-shift mobility-shift JJ 614 622 analysis analysis NN 623 625 of of IN 626 633 nuclear nuclear JJ 634 642 extracts extract NNS 642 643 . . . 644 648 This this DT 649 656 nuclear nuclear JJ 657 665 NF-kappa NF-kappa NNP 666 667 B B NNP 668 671 was be VBD 672 677 still still RB 678 685 present present JJ 686 690 when when WRB 691 702 contaminant contaminant JJ 703 706 LPS lps NN 707 710 was be VBD 711 718 removed remove VBN 719 721 by by IN 722 737 ultrafiltration ultrafiltration NN 738 741 and and CC 742 746 when when WRB 747 752 serum serum NN 753 756 was be VBD 757 764 omitted omit VBN 764 765 . . . 766 777 Protein-DNA protein-dna JJ 778 787 complexes complex NNS 788 790 of of IN 791 803 constitutive constitutive JJ 804 812 NF-kappa NF-kappa NNP 813 814 B B NNP 815 818 are be VBP 819 826 similar similar JJ 827 829 in in IN 830 838 mobility mobility NN 839 841 to to TO 842 845 the the DT 846 857 LPS-induced lps-induced JJ 858 866 NF-kappa NF-kappa NNP 867 868 B B NNP 869 872 and and CC 873 877 both both DT 878 881 are be VBP 882 892 recognized recognize VBN 893 895 by by IN 896 898 an an DT 899 907 antibody antibody NN 908 916 specific specific JJ 917 919 to to TO 920 923 the the DT 924 927 p50 p50 NN 928 935 subunit subunit NN 936 938 of of IN 939 947 NF-kappa NF-kappa NNP 948 950 B. B. NNP 951 953 By by IN 954 962 contrast contrast NN 962 963 , , , 964 973 treatment treatment NN 974 976 of of IN 977 982 cells cell NNS 983 987 with with IN 988 999 pyrrolidine pyrrolidine NN 1000 1015 dithiocarbamate dithiocarbamate NN 1016 1017 ( ( ( 1017 1021 PDTC PDTC NNP 1021 1022 ) ) ) 1023 1027 will will MD 1028 1032 only only RB 1033 1038 block block VB 1039 1050 LPS-induced lps-induced JJ 1051 1059 NF-kappa NF-kappa NNP 1060 1061 B B NNP 1061 1062 , , , 1063 1066 but but CC 1067 1070 not not RB 1071 1074 the the DT 1075 1087 constitutive constitutive JJ 1088 1095 binding bind VBG 1096 1103 protein protein NN 1103 1104 . . . 1105 1110 Using use VBG 1111 1119 LPS-free lps-free JJ 1120 1123 and and CC 1124 1134 serum-free serum-free JJ 1135 1145 conditions condition NNS 1145 1146 , , , 1147 1159 constitutive constitutive JJ 1160 1168 NF-kappa NF-kappa NNP 1169 1170 B B NNP 1171 1174 can can MD 1175 1177 be be VB 1178 1186 detected detect VBN 1187 1189 in in IN 1190 1199 different different JJ 1200 1204 cell cell NN 1205 1210 lines line NNS 1211 1213 of of IN 1214 1217 the the DT 1218 1227 monocytic monocytic JJ 1228 1235 lineage lineage NN 1236 1237 ( ( ( 1237 1241 HL60 HL60 NNP 1241 1242 , , , 1243 1247 U937 U937 NNP 1247 1248 , , , 1249 1254 THP-1 THP-1 NNP 1254 1255 , , , 1256 1260 Mono Mono NNP 1261 1264 Mac Mac NNP 1265 1266 1 1 CD 1267 1270 and and CC 1271 1275 Mono Mono NNP 1276 1279 Mac Mac NNP 1280 1281 6 6 CD 1281 1282 ) ) ) 1282 1283 , , , 1284 1287 but but CC 1288 1291 not not RB 1292 1294 in in IN 1295 1299 Molt Molt NNP 1300 1301 4 4 CD 1302 1303 T t NN 1304 1309 cells cell NNS 1310 1312 or or CC 1313 1317 K562 k562 NN 1318 1322 stem stem NN 1323 1328 cells cell NNS 1328 1329 . . . 1330 1334 When when WRB 1335 1342 ordered order VBN 1343 1352 according accord VBG 1353 1355 to to TO 1356 1361 stage stage NN 1362 1364 of of IN 1365 1375 maturation maturation NN 1375 1376 , , , 1377 1380 the the DT 1381 1387 amount amount NN 1388 1390 of of IN 1391 1403 constitutive constitutive JJ 1404 1412 NF-kappa NF-kappa NNP 1413 1414 B B NNP 1415 1418 was be VBD 1419 1422 not not RB 1423 1432 increased increase VBN 1433 1435 in in IN 1436 1440 more more RBR 1441 1447 mature mature JJ 1448 1452 cell cell NN 1453 1458 lines line NNS 1458 1459 . . . 1460 1471 Furthermore furthermore RB 1471 1472 , , , 1473 1477 when when WRB 1478 1486 inducing induce VBG 1487 1502 differentiation differentiation NN 1503 1505 in in IN 1506 1510 Mono Mono NNP 1511 1514 Mac Mac NNP 1515 1516 6 6 CD 1517 1522 cells cell NNS 1522 1523 , , , 1524 1528 with with IN 1529 1536 vitamin vitamin NN 1537 1539 D3 d3 NN 1539 1540 , , , 1541 1543 no no DT 1544 1550 change change NN 1551 1553 in in IN 1554 1566 constitutive constitutive JJ 1567 1569 or or CC 1570 1579 inducible inducible JJ 1580 1588 NF-kappa NF-kappa NNP 1589 1590 B B NNP 1591 1594 can can MD 1595 1597 be be VB 1598 1606 detected detect VBN 1606 1607 . . . 1608 1616 Analysis Analysis NNP 1617 1619 of of IN 1620 1627 primary primary JJ 1628 1633 cells cell NNS 1634 1642 revealed reveal VBD 1643 1654 substantial substantial JJ 1655 1667 constitutive constitutive JJ 1668 1676 NF-kappa NF-kappa NNP 1677 1686 B-binding b-binding JJ 1687 1695 activity activity NN 1696 1698 in in IN 1699 1704 blood blood NN 1705 1714 monocytes monocyte NNS 1714 1715 , , , 1716 1723 pleural pleural JJ 1724 1735 macrophages macrophage NNS 1736 1739 and and CC 1740 1748 alveolar alveolar JJ 1749 1760 macrophages macrophage NNS 1760 1761 . . . 1762 1765 The the DT 1766 1778 constitutive constitutive JJ 1779 1787 NF-kappa NF-kappa NNP 1788 1789 B B NNP 1790 1797 appears appear VBZ 1798 1800 to to TO 1801 1803 be be VB 1804 1816 functionally functionally RB 1817 1823 active active JJ 1823 1824 , , , 1825 1830 since since IN 1831 1832 a a DT 1833 1836 low low JJ 1837 1842 level level NN 1843 1845 of of IN 1846 1852 tumour tumour NN 1853 1861 necrosis necrosis NN 1862 1868 factor factor NN 1869 1870 ( ( ( 1870 1873 TNF TNF NNP 1873 1874 ) ) ) 1875 1885 transcript transcript NN 1886 1888 is be VBZ 1889 1899 detectable detectable JJ 1900 1902 in in IN 1903 1912 monocytes monocyte NNS 1912 1913 , , , 1914 1917 and and CC 1918 1922 this this DT 1923 1928 level level NN 1929 1932 can can MD 1933 1935 be be VB 1936 1945 increased increase VBN 1946 1948 by by IN 1949 1957 blocking block VBG 1958 1968 transcript transcript NN 1969 1980 degradation degradation NN 1981 1986 using use VBG 1987 2000 cycloheximide cycloheximide NN 2000 2001 . . . 2002 2005 The the DT 2006 2011 level level NN 2012 2014 of of IN 2015 2027 constitutive constitutive JJ 2028 2036 NF-kappa NF-kappa NNP 2037 2038 B B NNP 2039 2041 in in IN 2042 2047 these these DT 2048 2053 cells cell NNS 2054 2056 is be VBZ 2057 2065 variable variable JJ 2066 2069 and and CC 2070 2072 is be VBZ 2073 2083 frequently frequently RB 2084 2089 found find VBN 2090 2092 to to TO 2093 2095 be be VB 2096 2101 lower low JJR 2102 2104 in in IN 2105 2108 the the DT 2109 2113 more more RBR 2114 2120 mature mature JJ 2121 2132 macrophages macrophage NNS 2132 2133 . . . 2134 2146 Constitutive constitutive JJ 2147 2155 NF-kappa NF-kappa NNP 2156 2157 B B NNP 2158 2161 was be VBD 2162 2165 not not RB 2166 2176 maintained maintain VBN 2177 2179 by by IN 2180 2189 autocrine autocrine JJ 2190 2196 action action NN 2197 2199 of of IN 2200 2209 cytokines cytokine NNS 2210 2213 TNF TNF NNP 2213 2214 , , , 2215 2226 interleukin interleukin NN 2227 2228 6 6 CD 2228 2229 , , , 2230 2241 interleukin interleukin NN 2242 2244 10 10 CD 2244 2245 , , , 2246 2268 granulocyte-macrophage granulocyte-macrophage JJ 2269 2287 colony-stimulating colony-stimulating JJ 2288 2294 factor factor NN 2295 2297 or or CC 2298 2308 macrophage macrophage NN 2309 2327 colony-stimulating colony-stimulating JJ 2328 2334 factor factor NN 2334 2335 , , , 2336 2341 since since IN 2342 2354 neutralizing neutralize VBG 2355 2365 antibodies antibody NNS 2366 2369 did do VBD 2370 2373 not not RB 2374 2380 reduce reduce VB 2381 2393 constitutive constitutive JJ 2394 2405 DNA-binding dna-binding JJ 2406 2414 activity activity NN 2414 2415 . . . 2416 2427 Furthermore furthermore RB 2427 2428 , , , 2429 2437 blockade blockade NN 2438 2440 of of IN 2441 2454 prostaglandin prostaglandin NN 2455 2457 or or CC 2458 2469 leukotriene leukotriene NN 2470 2482 biosynthesis biosynthesis NN 2483 2486 did do VBD 2487 2490 not not RB 2491 2497 affect affect VB 2498 2510 constitutive constitutive JJ 2511 2519 NF-kappa NF-kappa NNP 2520 2522 B. B. NNP 2523 2524 ( ( ( 2524 2532 ABSTRACT ABSTRACT NNP 2533 2542 TRUNCATED truncated VBN 2543 2545 AT at IN 2546 2549 400 400 CD 2550 2555 WORDS words NNS 2555 2556 ) ) )