0 10 Triggering triggering NN 11 13 of of IN 14 17 the the DT 18 23 human human JJ 24 37 interleukin-6 interleukin-6 NN 38 42 gene gene NN 43 45 by by IN 46 62 interferon-gamma interferon-gamma NN 63 66 and and CC 67 72 tumor tumor NN 73 81 necrosis necrosis NN 82 94 factor-alpha factor-alpha NN 95 97 in in IN 98 107 monocytic monocytic JJ 108 113 cells cell NNS 114 122 involves involve VBZ 123 134 cooperation cooperation NN 135 142 between between IN 143 153 interferon interferon NN 154 164 regulatory regulatory JJ 165 173 factor-1 factor-1 NN 173 174 , , , 175 177 NF NF NNP 178 183 kappa kappa NN 184 185 B B NNP 185 186 , , , 187 190 and and CC 191 194 Sp1 sp1 NN 195 208 transcription transcription NN 209 216 factors factor NNS 216 217 . . . 219 221 We we PRP 222 234 investigated investigate VBD 235 238 the the DT 239 248 molecular molecular JJ 249 254 basis basis NN 255 257 of of IN 258 261 the the DT 262 273 synergistic synergistic JJ 274 283 induction induction NN 284 286 by by IN 287 303 interferon-gamma interferon-gamma NN 304 305 ( ( ( 305 321 IFN-gamma)/tumor ifn-gamma)/tumor NN 322 330 necrosis necrosis NN 331 343 factor-alpha factor-alpha NN 344 345 ( ( ( 345 354 TNF-alpha TNF-alpha NNP 354 355 ) ) ) 356 358 of of IN 359 364 human human JJ 365 378 interleukin-6 interleukin-6 NN 379 380 ( ( ( 380 384 IL-6 il-6 NN 384 385 ) ) ) 386 390 gene gene NN 391 393 in in IN 394 399 THP-1 thp-1 NN 400 409 monocytic monocytic JJ 410 415 cells cell NNS 415 416 , , , 417 420 and and CC 421 429 compared compare VBD 430 432 it it PRP 433 437 with with IN 438 441 the the DT 442 447 basis basis NN 448 450 of of IN 451 455 this this DT 456 465 induction induction NN 466 468 by by IN 469 487 lipopolysaccharide lipopolysaccharide NN 488 489 ( ( ( 489 492 LPS LPS NNP 492 493 ) ) ) 493 494 . . . 495 505 Functional functional JJ 506 513 studies study NNS 514 518 with with IN 519 523 IL-6 IL-6 NNP 524 532 promoter promoter NN 533 545 demonstrated demonstrate VBD 546 550 that that IN 551 556 three three CD 557 564 regions region NNS 565 568 are be VBP 569 572 the the DT 573 580 targets target NNS 581 583 of of IN 584 587 the the DT 588 597 IFN-gamma IFN-gamma NNP 598 604 and/or and/or CC 605 614 TNF-alpha TNF-alpha NNP 615 621 action action NN 621 622 , , , 623 630 whereas whereas IN 631 635 only only RB 636 639 one one CD 640 642 of of IN 643 648 these these DT 649 656 regions region NNS 657 663 seemed seem VBD 664 666 to to TO 667 669 be be VB 670 680 implicated implicate VBN 681 683 in in IN 684 687 LPS LPS NNP 688 698 activation activation NN 698 699 . . . 700 703 The the DT 704 709 three three CD 710 717 regions region NNS 718 727 concerned concern VBN 728 731 are be VBP 731 732 : : : 733 734 1 1 LS 734 735 ) ) ) 736 737 a a DT 738 744 region region NN 745 752 between between IN 753 756 -73 -73 CD 757 760 and and CC 761 764 -36 -36 CD 764 765 , , , 766 771 which which WDT 772 774 is be VBZ 775 778 the the DT 779 786 minimal minimal JJ 787 794 element element NN 795 804 inducible inducible JJ 805 807 by by IN 808 811 LPS LPS NNP 812 814 or or CC 815 824 TNF-alpha TNF-alpha NNP 824 825 ; ; : 826 827 2 2 LS 827 828 ) ) ) 829 831 an an DT 832 839 element element NN 840 847 located located JJ 848 855 between between IN 856 860 -181 -181 CD 861 864 and and CC 865 868 -73 -73 CD 868 869 , , , 870 875 which which WDT 876 884 appeared appear VBD 885 887 to to TO 888 896 regulate regulate VB 897 900 the the DT 901 909 response response NN 910 912 to to TO 913 922 IFN-gamma IFN-gamma NNP 923 926 and and CC 927 936 TNF-alpha TNF-alpha NNP 937 947 negatively negatively RB 947 948 ; ; : 949 952 and and CC 953 954 3 3 LS 954 955 ) ) ) 956 957 a a DT 958 964 distal distal JJ 965 972 element element NN 973 981 upstream upstream JJ 982 984 of of IN 985 989 -224 -224 CD 989 990 , , , 991 996 which which WDT 997 1000 was be VBD 1001 1010 inducible inducible JJ 1011 1013 by by IN 1014 1023 IFN-gamma IFN-gamma NNP 1024 1029 alone alone RB 1029 1030 . . . 1031 1034 LPS lps NN 1035 1044 signaling signaling NN 1045 1048 was be VBD 1049 1054 found find VBN 1055 1057 to to TO 1058 1065 involve involve VB 1066 1068 NF NF NNP 1069 1074 kappa kappa NN 1075 1076 B B NNP 1077 1087 activation activation NN 1088 1090 by by IN 1091 1094 the the DT 1095 1102 p50/p65 p50/p65 NN 1103 1115 heterodimers heterodimer NNS 1115 1116 . . . 1117 1128 Synergistic synergistic JJ 1129 1138 induction induction NN 1139 1141 of of IN 1142 1145 the the DT 1146 1150 IL-6 il-6 NN 1151 1155 gene gene NN 1156 1158 by by IN 1159 1168 IFN-gamma IFN-gamma NNP 1169 1172 and and CC 1173 1182 TNF-alpha TNF-alpha NNP 1182 1183 , , , 1184 1186 in in IN 1187 1196 monocytic monocytic JJ 1197 1202 cells cell NNS 1202 1203 , , , 1204 1212 involved involve VBN 1213 1224 cooperation cooperation NN 1225 1232 between between IN 1233 1236 the the DT 1237 1242 IRF-1 IRF-1 NNP 1243 1246 and and CC 1247 1249 NF NF NNP 1250 1255 kappa kappa NN 1256 1257 B B NNP 1258 1261 p65 p65 NN 1262 1272 homodimers homodimer NNS 1273 1277 with with IN 1278 1289 concomitant concomitant JJ 1290 1297 removal removal NN 1298 1300 of of IN 1301 1304 the the DT 1305 1313 negative negative JJ 1314 1320 effect effect NN 1321 1323 of of IN 1324 1327 the the DT 1328 1342 retinoblastoma retinoblastoma NN 1343 1350 control control NN 1351 1358 element element NN 1359 1366 present present JJ 1367 1369 in in IN 1370 1373 the the DT 1374 1378 IL-6 il-6 NN 1379 1387 promoter promoter NN 1387 1388 . . . 1389 1393 This this DT 1394 1401 removal removal NN 1402 1410 occurred occur VBD 1411 1413 by by IN 1414 1424 activation activation NN 1425 1427 of of IN 1428 1431 the the DT 1432 1444 constitutive constitutive JJ 1445 1448 Sp1 sp1 NN 1449 1455 factor factor NN 1455 1456 , , , 1457 1462 whose whose WP$ 1463 1472 increased increase VBD 1473 1480 binding binding NN 1481 1489 activity activity NN 1490 1493 and and CC 1494 1509 phosphorylation phosphorylation NN 1510 1514 were be VBD 1515 1523 mediated mediate VBN 1524 1526 by by IN 1527 1536 IFN-gamma IFN-gamma NNP 1536 1537 . . .