0 5 Tumor tumor NN 6 14 necrosis necrosis NN 15 27 factor-alpha factor-alpha NN 28 32 mRNA mrna NN 33 45 accumulation accumulation NN 46 48 in in IN 49 54 human human JJ 55 69 myelomonocytic myelomonocytic JJ 70 74 cell cell NN 75 80 lines line NNS 80 81 . . . 82 86 Role role NN 87 89 of of IN 90 105 transcriptional transcriptional JJ 106 116 regulation regulation NN 117 119 by by IN 120 123 DNA DNA NNP 124 132 sequence sequence NN 133 139 motifs motif NNS 140 143 and and CC 144 148 mRNA mrna NN 149 162 stabilization stabilization NN 162 163 . . . 165 168 The the DT 169 177 cytokine cytokine NN 178 181 TNF tnf NN 182 190 mediates mediate VBZ 191 195 many many JJ 196 198 of of IN 199 202 the the DT 203 213 pathologic pathologic JJ 214 219 signs sign NNS 220 222 of of IN 223 231 cachexia cachexia NN 231 232 , , , 233 245 inflammation inflammation NN 245 246 , , , 247 250 and and CC 251 257 sepsis sepsis NN 257 258 . . . 259 262 The the DT 263 270 current current JJ 271 275 work work NN 276 285 describes describe VBZ 286 289 the the DT 290 300 regulation regulation NN 301 303 of of IN 304 307 TNF TNF NNP 308 310 in in IN 311 316 human human JJ 317 331 myelomonocytic myelomonocytic JJ 332 336 cell cell NN 337 342 lines line NNS 343 348 after after IN 349 352 PMA PMA NNP 353 364 stimulation stimulation NN 364 365 . . . 366 369 The the DT 370 374 cell cell NN 375 380 lines line NNS 381 388 exhibit exhibit VBP 389 390 a a DT 391 394 low low JJ 395 400 level level NN 401 403 of of IN 404 416 constitutive constitutive JJ 417 420 TNF TNF NNP 421 425 mRNA mrna NN 426 436 expression expression NN 436 437 . . . 438 444 Within within IN 445 446 2 2 CD 447 449 to to TO 450 451 4 4 CD 452 453 h h NN 454 456 of of IN 457 460 PMA PMA NNP 461 469 exposure exposure NN 469 470 , , , 471 477 steady steady JJ 478 483 state state NN 484 490 levels level NNS 491 493 of of IN 494 497 TNF TNF NNP 498 502 mRNA mRNA NNP 503 506 are be VBP 507 515 markedly markedly RB 516 524 elevated elevated JJ 525 527 in in IN 528 531 all all DT 532 546 myelomonocytic myelomonocytic JJ 547 551 cell cell NN 552 557 lines line NNS 558 565 studied study VBN 565 566 . . . 567 571 This this DT 572 576 rise rise NN 577 579 is be VBZ 580 583 due due JJ 584 586 to to TO 587 596 increased increase VBN 597 601 mRNA mrna NN 602 611 stability stability NN 611 612 , , , 613 618 which which WDT 619 628 increased increase VBD 629 631 by by IN 632 638 almost almost RB 639 646 twofold twofold RB 646 647 , , , 648 651 and and CC 652 654 to to TO 655 657 an an DT 658 665 overall overall JJ 666 674 increase increase NN 675 677 in in IN 678 691 transcription transcription NN 691 692 , , , 693 698 which which WDT 699 704 rises rise VBZ 705 707 by by IN 708 712 more more JJR 713 717 than than IN 718 725 sixfold sixfold RB 725 726 . . . 727 729 At at IN 730 733 the the DT 734 739 level level NN 740 742 of of IN 743 746 the the DT 747 754 genomic genomic JJ 755 758 TNF tnf NN 759 763 gene gene NN 763 764 , , , 765 766 a a DT 767 772 DNase DNase NNP 773 774 I i CD 775 789 hypersensitive hypersensitive JJ 790 794 site site NN 795 797 is be VBZ 798 806 detected detect VBN 807 813 within within IN 814 817 the the DT 818 821 TNF TNF NNP 822 830 promoter promoter NN 831 838 between between IN 839 843 -200 -200 CD 844 846 to to TO 847 851 -100 -100 CD 852 854 bp bp NN 855 863 relative relative JJ 864 866 to to TO 867 870 the the DT 871 884 transcription transcription NN 885 895 initiation initiation NN 896 900 site site NN 900 901 . . . 902 910 Although although IN 911 917 absent absent JJ 918 920 in in IN 921 934 nonexpressing nonexpresse VBG 935 950 erythroleukemia erythroleukemia NN 951 955 cell cell NN 956 961 lines line NNS 961 962 , , , 963 966 the the DT 967 972 DNase DNase NNP 973 974 I i CD 975 979 site site NN 980 982 is be VBZ 983 990 present present JJ 991 993 in in IN 994 1003 uninduced uninduced JJ 1004 1018 myelomonocytic myelomonocytic JJ 1019 1023 cell cell NN 1024 1029 lines line NNS 1030 1033 and and CC 1034 1036 is be VBZ 1037 1040 not not RB 1041 1048 changed change VBN 1049 1054 after after IN 1055 1058 PMA PMA NNP 1059 1068 induction induction NN 1068 1069 . . . 1070 1073 The the DT 1074 1077 PMA PMA NNP 1078 1087 induction induction NN 1088 1090 of of IN 1091 1096 c-fos c-fos NN 1097 1101 mRNA mrna NN 1102 1112 correlated correlate VBD 1113 1117 well well RB 1118 1122 with with IN 1123 1126 TNF TNF NNP 1127 1131 gene gene NN 1132 1141 induction induction NN 1141 1142 ; ; : 1143 1153 expression expression NN 1154 1156 of of IN 1157 1162 genes gene NNS 1163 1171 encoding encode VBG 1172 1177 other other JJ 1178 1186 proteins protein NNS 1187 1189 in in IN 1190 1193 the the DT 1194 1198 AP-1 ap-1 NN 1199 1206 complex complex NN 1207 1208 ( ( ( 1208 1212 junB junb NN 1213 1216 and and CC 1217 1221 junD jund NN 1221 1222 ) ) ) 1223 1227 were be VBD 1228 1232 also also RB 1233 1240 induced induce VBN 1241 1243 by by IN 1244 1247 PMA PMA NNP 1247 1248 . . . 1249 1252 The the DT 1253 1260 nuclear nuclear JJ 1261 1269 extracts extract NNS 1270 1274 from from IN 1275 1282 resting rest VBG 1283 1286 and and CC 1287 1294 induced induce VBN 1295 1299 ML-1 ml-1 NN 1300 1305 cells cell NNS 1306 1313 contain contain VBP 1314 1322 proteins protein NNS 1323 1330 binding bind VBG 1331 1343 specifically specifically RB 1344 1346 to to TO 1347 1350 the the DT 1351 1355 AP-1 ap-1 NN 1355 1356 , , , 1357 1361 AP-2 ap-2 NN 1361 1362 , , , 1363 1366 and and CC 1367 1369 NF NF NNP 1370 1375 kappa kappa NN 1376 1377 B B NNP 1378 1386 sequence sequence NN 1387 1394 located located JJ 1395 1401 within within IN 1402 1405 the the DT 1406 1409 TNF TNF NNP 1410 1418 promoter promoter NN 1418 1419 . . . 1420 1423 PMA PMA NNP 1424 1433 induction induction NN 1434 1443 increases increase VBZ 1444 1447 the the DT 1448 1453 level level NN 1454 1456 of of IN 1457 1458 a a DT 1459 1465 number number NN 1466 1468 of of IN 1469 1477 specific specific JJ 1478 1485 binding bind VBG 1486 1495 complexes complex NNS 1496 1504 relative relative JJ 1505 1507 to to TO 1508 1511 the the DT 1512 1519 resting rest VBG 1520 1525 cells cell NNS 1525 1526 . . . 1527 1530 The the DT 1531 1541 regulatory regulatory JJ 1542 1552 mechanisms mechanism NNS 1553 1555 of of IN 1556 1559 the the DT 1560 1565 human human JJ 1566 1569 and and CC 1570 1576 murine murine JJ 1577 1580 TNF tnf NN 1581 1586 genes gene NNS 1587 1590 are be VBP 1591 1600 discussed discuss VBN 1600 1601 . . .