0 1 A a DT 2 7 novel novel JJ 8 34 lipopolysaccharide-induced lipopolysaccharide-induced JJ 35 48 transcription transcription NN 49 55 factor factor NN 56 66 regulating regulate VBG 67 72 tumor tumor NN 73 81 necrosis necrosis NN 82 88 factor factor NN 89 94 alpha alpha NN 95 99 gene gene NN 100 110 expression expression NN 110 111 : : : 112 121 molecular molecular JJ 122 129 cloning cloning NN 129 130 , , , 131 141 sequencing sequencing NN 141 142 , , , 143 159 characterization characterization NN 159 160 , , , 161 164 and and CC 165 176 chromosomal chromosomal JJ 177 187 assignment assignment NN 187 188 . . . 190 208 Lipopolysaccharide Lipopolysaccharide NNP 209 210 ( ( ( 210 213 LPS LPS NNP 213 214 ) ) ) 215 217 is be VBZ 218 219 a a DT 220 226 potent potent JJ 227 237 stimulator stimulator NN 238 240 of of IN 241 250 monocytes monocyte NNS 251 254 and and CC 255 266 macrophages macrophage NNS 266 267 , , , 268 275 causing cause VBG 276 285 secretion secretion NN 286 288 of of IN 289 294 tumor tumor NN 295 303 necrosis necrosis NN 304 310 factor factor NN 311 316 alpha alpha NN 317 318 ( ( ( 318 327 TNF-alpha TNF-alpha NNP 327 328 ) ) ) 329 332 and and CC 333 338 other other JJ 339 351 inflammatory inflammatory JJ 352 361 mediators mediator NNS 361 362 . . . 363 368 Given give VBN 369 372 the the DT 373 384 deleterious deleterious JJ 385 392 effects effect NNS 393 395 to to TO 396 399 the the DT 400 404 host host NN 405 407 of of IN 408 417 TNF-alpha TNF-alpha NNP 417 418 , , , 419 421 it it PRP 422 425 has have VBZ 426 430 been be VBN 431 441 postulated postulate VBN 442 446 that that IN 447 456 TNF-alpha TNF-alpha NNP 457 461 gene gene NN 462 472 expression expression NN 473 477 must must MD 478 480 be be VB 481 488 tightly tightly RB 489 498 regulated regulate VBN 498 499 . . . 500 503 The the DT 504 510 nature nature NN 511 513 of of IN 514 517 the the DT 518 525 nuclear nuclear JJ 526 535 factor(s) factor(s) NN 536 540 that that WDT 541 548 control control VBP 549 558 TNF-alpha TNF-alpha NNP 559 563 gene gene NN 564 577 transcription transcription NN 578 580 in in IN 581 587 humans human NNS 588 595 remains remain VBZ 596 603 obscure obscure JJ 603 604 , , , 605 613 although although IN 614 623 NF-kappaB NF-kappaB NNP 624 627 has have VBZ 628 632 been be VBN 633 642 suggested suggest VBN 642 643 . . . 644 647 Our our PRP$ 648 656 previous previous JJ 657 664 studies study NNS 665 675 pertaining pertain VBG 676 678 to to TO 679 689 macrophage macrophage NN 690 698 response response NN 699 701 to to TO 702 705 LPS LPS NNP 706 716 identified identify VBD 717 718 a a DT 719 724 novel novel JJ 725 736 DNA-binding dna-binding JJ 737 743 domain domain NN 744 751 located located JJ 752 756 from from IN 757 761 -550 -550 CD 762 764 to to TO 765 769 -487 -487 CD 770 772 in in IN 773 776 the the DT 777 782 human human JJ 783 792 TNF-alpha TNF-alpha NNP 793 801 promoter promoter NN 802 806 that that WDT 807 815 contains contain VBZ 816 831 transcriptional transcriptional JJ 832 840 activity activity NN 840 841 , , , 842 845 but but CC 846 851 lacks lack VBZ 852 855 any any DT 856 861 known known JJ 862 879 NF-kappaB-binding nf-kappab-binding JJ 880 885 sites site NNS 885 886 . . . 887 889 We we PRP 890 894 have have VBP 895 899 used use VBN 900 904 this this DT 905 908 DNA dna NN 909 917 fragment fragment NN 918 920 to to TO 921 928 isolate isolate VB 929 932 and and CC 933 939 purify purify VB 940 941 a a DT 942 948 60-kDa 60-kda JJ 949 956 protein protein NN 957 964 binding bind VBG 965 967 to to TO 968 972 this this DT 973 981 fragment fragment NN 982 985 and and CC 986 994 obtained obtain VBN 995 998 its its PRP$ 999 1013 amino-terminal amino-terminal JJ 1014 1022 sequence sequence NN 1022 1023 , , , 1024 1029 which which WDT 1030 1033 was be VBD 1034 1038 used use VBN 1039 1041 to to TO 1042 1048 design design VB 1049 1059 degenerate degenerate JJ 1060 1066 probes probe NNS 1067 1069 to to TO 1070 1076 screen screen VB 1077 1078 a a DT 1079 1083 cDNA cdna NN 1084 1091 library library NN 1092 1096 from from IN 1097 1102 THP-1 thp-1 NN 1103 1108 cells cell NNS 1108 1109 . . . 1110 1111 A a DT 1112 1117 novel novel JJ 1118 1122 cDNA cdna NN 1123 1128 clone clone NN 1129 1130 ( ( ( 1130 1133 1.8 1.8 CD 1134 1136 kb kb NN 1136 1137 ) ) ) 1138 1141 was be VBD 1142 1150 isolated isolate VBN 1151 1154 and and CC 1155 1160 fully fully RB 1161 1170 sequenced sequence VBN 1170 1171 . . . 1172 1188 Characterization characterization NN 1189 1191 of of IN 1192 1196 this this DT 1197 1201 cDNA cdna NN 1202 1207 clone clone NN 1208 1216 revealed reveal VBD 1217 1221 that that IN 1222 1225 its its PRP$ 1226 1235 induction induction NN 1236 1239 was be VBD 1240 1249 dependent dependent JJ 1250 1252 on on IN 1253 1256 LPS LPS NNP 1257 1267 activation activation NN 1268 1270 of of IN 1271 1276 THP-1 thp-1 NN 1277 1282 cells cell NNS 1282 1283 ; ; : 1284 1289 hence hence RB 1289 1290 , , , 1291 1294 the the DT 1295 1299 name name NN 1300 1311 LPS-induced lps-induced JJ 1312 1321 TNF-alpha TNF-alpha NNP 1322 1328 factor factor NN 1329 1330 ( ( ( 1330 1335 LITAF LITAF NNP 1335 1336 ) ) ) 1336 1337 . . . 1338 1348 Inhibition Inhibition NNP 1349 1351 of of IN 1352 1357 LITAF LITAF NNP 1358 1362 mRNA mRNA NNP 1363 1373 expression expression NN 1374 1376 in in IN 1377 1382 THP-1 thp-1 NN 1383 1388 cells cell NNS 1389 1397 resulted result VBD 1398 1400 in in IN 1401 1402 a a DT 1403 1412 reduction reduction NN 1413 1415 of of IN 1416 1425 TNF-alpha TNF-alpha NNP 1426 1437 transcripts transcript NNS 1437 1438 . . . 1439 1441 In in IN 1442 1450 addition addition NN 1450 1451 , , , 1452 1456 high high JJ 1457 1462 level level NN 1463 1465 of of IN 1466 1476 expression expression NN 1477 1479 of of IN 1480 1485 LITAF LITAF NNP 1486 1490 mRNA mRNA NNP 1491 1494 was be VBD 1495 1503 observed observe VBN 1504 1517 predominantly predominantly RB 1518 1520 in in IN 1521 1524 the the DT 1525 1533 placenta placenta NN 1533 1534 , , , 1535 1545 peripheral peripheral JJ 1546 1551 blood blood NN 1552 1562 leukocytes leukocyte NNS 1562 1563 , , , 1564 1569 lymph lymph NN 1570 1575 nodes node NNS 1575 1576 , , , 1577 1580 and and CC 1581 1584 the the DT 1585 1591 spleen spleen NN 1591 1592 . . . 1593 1600 Finally finally RB 1600 1601 , , , 1602 1613 chromosomal chromosomal JJ 1614 1626 localization localization NN 1627 1632 using use VBG 1633 1645 fluorescence fluorescence NN 1646 1648 in in FW 1649 1653 situ situ FW 1654 1667 hybridization hybridization NN 1668 1676 revealed reveal VBD 1677 1681 that that IN 1682 1687 LITAF LITAF NNP 1688 1694 mapped map VBN 1695 1697 to to TO 1698 1708 chromosome chromosome NN 1709 1722 16p12-16p13.3 16p12-16p13.3 NN 1722 1723 . . . 1724 1732 Together together RB 1732 1733 , , , 1734 1739 these these DT 1740 1748 findings finding NNS 1749 1756 suggest suggest VBP 1757 1761 that that IN 1762 1767 LITAF LITAF NNP 1768 1773 plays play VBZ 1774 1776 an an DT 1777 1786 important important JJ 1787 1791 role role NN 1792 1794 in in IN 1795 1798 the the DT 1799 1809 activation activation NN 1810 1812 of of IN 1813 1816 the the DT 1817 1822 human human JJ 1823 1832 TNF-alpha TNF-alpha NNP 1833 1837 gene gene NN 1838 1841 and and CC 1842 1850 proposes propose VBZ 1851 1852 a a DT 1853 1856 new new JJ 1857 1866 mechanism mechanism NN 1867 1869 to to TO 1870 1877 control control VB 1878 1887 TNF-alpha TNF-alpha NNP 1888 1892 gene gene NN 1893 1903 expression expression NN 1903 1904 . . .