0 10 Activation Activation NNP 11 13 of of IN 14 17 the the DT 18 29 interleukin interleukin NN 30 31 6 6 CD 32 36 gene gene NN 37 39 by by IN 40 53 Mycobacterium Mycobacterium NNP 54 66 tuberculosis tuberculosis NN 67 69 or or CC 70 88 lipopolysaccharide lipopolysaccharide NN 89 91 is be VBZ 92 100 mediated mediate VBN 101 103 by by IN 104 111 nuclear nuclear JJ 112 119 factors factor NNS 120 126 NF-IL6 NF-IL6 NNP 127 130 and and CC 131 139 NF-kappa NF-kappa NNP 140 141 B B NNP 142 143 [ [ ( 143 152 published publish VBN 153 160 erratum erratum NN 161 168 appears appear VBZ 169 171 in in IN 172 176 Proc Proc NNP 177 181 Natl Natl NNP 182 186 Acad Acad NNP 187 190 Sci Sci NNP 191 192 U U NNP 193 194 S S NNP 195 196 A A NNP 197 201 1995 1995 CD 202 205 Apr apr IN 206 219 11;92(8):3632 11;92(8):3632 CD 219 220 ] ] ) 222 225 The the DT 226 230 host host NN 231 239 response response NN 240 242 to to TO 243 256 Mycobacterium Mycobacterium NNP 257 269 tuberculosis tuberculosis NN 270 278 includes include VBZ 279 288 granuloma granuloma NN 289 298 formation formation NN 299 301 at at IN 302 307 sites site NNS 308 310 of of IN 311 320 infection infection NN 321 324 and and CC 325 333 systemic systemic JJ 334 342 symptoms symptom NNS 342 343 . . . 344 353 Cytokines Cytokine NNPS 354 358 have have VBP 359 363 been be VBN 364 374 identified identify VBN 375 377 by by IN 378 398 immunohistochemistry immunohistochemistry NN 399 401 in in IN 402 412 granulomas granuloma NNS 413 415 in in IN 416 422 animal animal NN 423 429 models model NNS 430 432 of of IN 433 441 bacillus bacillus NN 442 457 Calmette-Guerin Calmette-Guerin NNP 458 459 ( ( ( 459 462 BCG BCG NNP 462 463 ) ) ) 464 473 infection infection NN 474 477 and and CC 478 481 are be VBP 482 490 released release VBN 491 493 by by IN 494 505 mononuclear mononuclear JJ 506 516 phagocytes phagocyte NNS 517 521 upon upon IN 522 533 stimulation stimulation NN 534 536 by by IN 537 550 mycobacterial mycobacterial JJ 551 559 proteins protein NNS 559 560 . . . 561 563 In in IN 564 568 this this DT 569 575 regard regard NN 575 576 , , , 577 580 the the DT 581 589 cytokine cytokine NN 590 601 interleukin interleukin NN 602 603 6 6 CD 604 605 ( ( ( 605 609 IL-6 il-6 NN 609 610 ) ) ) 611 614 may may MD 615 619 play play VB 620 621 a a DT 622 626 role role NN 627 629 in in IN 630 633 the the DT 634 642 clinical clinical JJ 643 657 manifestations manifestation NNS 658 661 and and CC 662 674 pathological pathological JJ 675 681 events event NNS 682 684 of of IN 685 697 tuberculosis tuberculosis NN 698 707 infection infection NN 707 708 . . . 709 711 We we PRP 712 716 have have VBP 717 729 demonstrated demonstrate VBN 730 734 that that IN 735 752 lipoarabinomannan lipoarabinomannan NN 753 754 ( ( ( 754 757 LAM LAM NNP 757 758 ) ) ) 759 763 from from IN 764 767 the the DT 768 781 mycobacterial mycobacterial JJ 782 786 cell cell NN 787 791 wall wall NN 791 792 , , , 793 798 which which WDT 799 802 was be VBD 803 812 virtually virtually RB 813 819 devoid devoid JJ 820 822 of of IN 823 841 lipopolysaccharide lipopolysaccharide NN 842 843 ( ( ( 843 846 LPS LPS NNP 846 847 ) ) ) 847 848 , , , 849 859 stimulated stimulate VBD 860 871 mononuclear mononuclear JJ 872 882 phagocytes phagocyte NNS 883 885 to to TO 886 893 release release VB 894 898 IL-6 il-6 NN 899 901 in in IN 902 903 a a DT 904 917 dose-response dose-response JJ 918 924 manner manner NN 924 925 . . . 926 929 LAM LAM NNP 930 933 and and CC 934 937 LPS LPS NNP 938 942 were be VBD 943 949 potent potent JJ 950 958 inducers inducer NNS 959 961 of of IN 962 966 IL-6 IL-6 NNP 967 971 gene gene NN 972 982 expression expression NN 983 985 in in IN 986 996 peripheral peripheral JJ 997 1002 blood blood NN 1003 1012 monocytes monocyte NNS 1012 1013 . . . 1014 1018 Both both CC 1019 1023 LAM- LAM- NNP 1024 1027 and and CC 1028 1041 LPS-inducible lps-inducible JJ 1042 1046 IL-6 IL-6 NNP 1047 1055 promoter promoter NN 1056 1064 activity activity NN 1065 1068 was be VBD 1069 1078 localized localized JJ 1079 1081 to to TO 1082 1083 a a DT 1084 1087 DNA DNA NNP 1088 1096 fragment fragment NN 1096 1097 , , , 1098 1107 positions position NNS 1108 1112 -158 -158 CD 1113 1115 to to TO 1116 1119 -49 -49 CD 1119 1120 , , , 1121 1123 by by IN 1124 1132 deletion deletion NN 1133 1141 analysis analysis NN 1142 1145 and and CC 1146 1161 chloramphenicol chloramphenicol NN 1162 1179 acetyltransferase acetyltransferase NN 1180 1185 assay assay NN 1185 1186 . . . 1187 1190 Two two CD 1191 1198 nuclear nuclear JJ 1199 1205 factor factor NN 1206 1212 NF-IL6 nf-il6 NN 1213 1214 ( ( ( 1214 1223 positions position NNS 1224 1228 -153 -153 CD 1229 1231 to to TO 1232 1236 -145 -145 CD 1237 1240 and and CC 1241 1244 -83 -83 CD 1245 1247 to to TO 1248 1251 -75 -75 CD 1251 1252 ) ) ) 1253 1256 and and CC 1257 1260 one one CD 1261 1268 nuclear nuclear JJ 1269 1275 factor factor NN 1276 1284 NF-kappa NF-kappa NNP 1285 1286 B B NNP 1287 1288 ( ( ( 1288 1297 positions position NNS 1298 1301 -72 -72 CD 1302 1304 to to TO 1305 1308 -63 -63 CD 1308 1309 ) ) ) 1310 1316 motifs motif NNS 1317 1320 are be VBP 1321 1328 present present JJ 1329 1335 within within IN 1336 1340 this this DT 1341 1349 fragment fragment NN 1349 1350 . . . 1351 1364 Site-directed site-directed JJ 1365 1376 mutagenesis mutagenesis NN 1377 1379 of of IN 1380 1383 one one CD 1384 1386 or or CC 1387 1391 more more JJR 1392 1394 of of IN 1395 1400 these these DT 1401 1407 motifs motif NNS 1408 1414 within within IN 1415 1418 the the DT 1419 1423 IL-6 il-6 NN 1424 1432 promoter promoter NN 1433 1445 demonstrated demonstrate VBD 1446 1450 that that IN 1451 1455 each each DT 1456 1459 has have VBZ 1460 1468 positive positive JJ 1469 1479 regulatory regulatory JJ 1480 1488 activity activity NN 1489 1492 and and CC 1493 1497 that that IN 1498 1502 they they PRP 1503 1508 could could MD 1509 1512 act act VB 1513 1515 in in IN 1516 1517 a a DT 1518 1527 function- function- NN 1528 1531 and and CC 1532 1555 orientation-independent orientation-independent JJ 1556 1562 manner manner NN 1562 1563 . . . 1564 1572 Deletion deletion NN 1573 1575 of of IN 1576 1579 all all DT 1580 1585 three three CD 1586 1594 elements element NNS 1595 1604 abolished abolish VBD 1605 1617 inducibility inducibility NN 1618 1620 of of IN 1621 1625 IL-6 IL-6 NNP 1626 1634 promoter promoter NN 1635 1643 activity activity NN 1644 1646 by by IN 1647 1651 both both CC 1652 1655 LAM LAM NNP 1656 1659 and and CC 1660 1663 LPS LPS NNP 1663 1664 . . . 1665 1667 We we PRP 1668 1676 conclude conclude VBP 1677 1681 that that IN 1682 1685 the the DT 1686 1692 NF-IL6 NF-IL6 NNP 1693 1696 and and CC 1697 1705 NF-kappa NF-kappa NNP 1706 1707 B B NNP 1708 1713 sites site NNS 1714 1721 mediate mediate VBP 1722 1726 IL-6 il-6 NN 1727 1736 induction induction NN 1737 1739 in in IN 1740 1748 response response NN 1749 1751 to to TO 1752 1756 both both CC 1757 1760 LPS LPS NNP 1761 1764 and and CC 1765 1768 LAM LAM NNP 1768 1769 , , , 1770 1776 acting act VBG 1777 1779 as as IN 1780 1789 bacterial bacterial JJ 1790 1792 or or CC 1793 1806 mycobacterial mycobacterial JJ 1807 1815 response response NN 1816 1824 elements element NNS 1824 1825 . . .