0 9 Induction Induction NNP 10 12 of of IN 13 27 interleukin-12 interleukin-12 NN 28 31 p40 p40 NN 32 42 transcript transcript NN 43 45 by by IN 46 50 CD40 cd40 NN 51 59 ligation ligation NN 60 63 via via IN 64 74 activation activation NN 75 77 of of IN 78 85 nuclear nuclear JJ 86 99 factor-kappaB factor-kappab NN 99 100 . . . 102 116 Interleukin-12 interleukin-12 NN 117 119 is be VBZ 120 128 produced produce VBN 129 131 in in IN 132 140 response response NN 141 143 to to TO 144 153 infection infection NN 154 158 with with IN 159 167 bacteria bacteria NNS 168 170 or or CC 171 180 parasites parasite NNS 181 183 or or CC 184 186 to to TO 187 196 bacterial bacterial JJ 197 209 constituents constituent NNS 210 214 such such JJ 215 217 as as IN 218 221 LPS lps NN 222 224 in in IN 225 246 monocytes/macrophages monocytes/macrophage NNS 247 250 and and CC 251 260 dendritic dendritic JJ 261 266 cells cell NNS 266 267 , , , 268 271 and and CC 272 276 also also RB 277 286 generated generate VBN 287 289 by by IN 290 293 the the DT 294 305 interaction interaction NN 306 313 between between IN 314 323 activated activate VBN 324 325 T t NN 326 331 cells cell NNS 332 335 and and CC 336 354 antigen-presenting antigen-presenting JJ 355 360 cells cell NNS 361 364 via via IN 365 374 CD40-CD40 CD40-CD40 NNP 375 381 ligand ligand NN 382 383 ( ( ( 383 388 CD40L CD40L NNP 388 389 ) ) ) 389 390 . . . 391 393 So so RB 394 397 far far RB 397 398 , , , 399 414 transcriptional transcriptional JJ 415 423 analyses analysis NNS 424 426 of of IN 427 430 p40 p40 NN 431 435 have have VBP 436 440 been be VBN 441 448 carried carry VBN 449 452 out out RP 453 457 only only RB 458 463 using use VBG 464 473 bacterial bacterial JJ 474 486 constituents constituent NNS 487 491 such such JJ 492 494 as as IN 495 498 LPS lps NN 499 501 as as IN 502 509 stimuli stimulus NNS 509 510 . . . 511 513 In in IN 514 517 the the DT 518 525 present present JJ 526 531 study study NN 531 532 , , , 533 535 we we PRP 536 540 have have VBP 541 554 characterized characterize VBN 555 558 the the DT 559 574 transcriptional transcriptional JJ 575 584 induction induction NN 585 587 of of IN 588 591 p40 p40 NN 592 594 by by IN 595 599 CD40 cd40 NN 600 608 ligation ligation NN 609 611 in in IN 612 613 a a DT 614 619 human human JJ 620 621 B B NNP 622 636 lymphoblastoid lymphoblastoid JJ 637 641 cell cell NN 642 646 line line NN 646 647 , , , 648 653 Daudi Daudi NNP 653 654 , , , 655 658 and and CC 659 660 a a DT 661 666 human human JJ 667 672 acute acute JJ 673 682 monocytic monocytic JJ 683 691 leukemia leukemia NN 692 696 cell cell NN 697 701 line line NN 701 702 , , , 703 708 THP-1 thp-1 NN 708 709 . . . 710 715 These these DT 716 721 cells cell NNS 721 722 , , , 723 733 stimulated stimulate VBN 734 736 by by IN 737 739 an an DT 740 749 agonistic agonistic JJ 750 760 monoclonal monoclonal JJ 761 769 antibody antibody NN 770 777 against against IN 778 782 CD40 CD40 NNP 783 785 or or CC 786 788 by by IN 789 801 transfection transfection NN 802 806 with with IN 807 808 a a DT 809 814 CD40L CD40L NNP 815 825 expression expression NN 826 832 vector vector NN 832 833 , , , 834 842 secreted secrete VBN 843 846 p40 p40 NN 847 850 and and CC 851 857 showed show VBD 858 866 enhanced enhance VBN 867 870 p40 p40 NN 871 875 mRNA mrna NN 876 886 expression expression NN 886 887 . . . 888 896 Sequence sequence NN 897 905 analysis analysis NN 906 908 of of IN 909 912 the the DT 913 916 p40 p40 NN 917 925 promoter promoter NN 926 932 region region NN 933 943 identified identify VBD 944 947 two two CD 948 957 potential potential JJ 958 965 nuclear nuclear JJ 966 972 factor factor NN 973 974 ( ( ( 974 984 NF)-kappaB NF)-kappaB NNP 985 992 binding binding NN 993 998 sites site NNS 999 1008 conserved conserve VBN 1009 1016 between between IN 1017 1022 mouse mouse NN 1023 1026 and and CC 1027 1032 human human NN 1032 1033 . . . 1034 1049 Electrophoretic electrophoretic JJ 1050 1058 mobility mobility NN 1059 1064 shift shift NN 1065 1070 assay assay NN 1071 1079 revealed reveal VBD 1080 1084 that that IN 1085 1088 the the DT 1089 1098 potential potential JJ 1099 1108 NF-kappaB NF-kappaB NNP 1109 1116 binding binding NN 1117 1125 sequence sequence NN 1126 1131 which which WDT 1132 1134 is be VBZ 1135 1142 located located JJ 1143 1149 around around IN 1150 1153 120 120 CD 1154 1156 bp bp NN 1157 1165 upstream upstream RB 1166 1168 of of IN 1169 1172 the the DT 1173 1186 transcription transcription NN 1187 1197 initiation initiation NN 1198 1202 site site NN 1203 1205 in in IN 1206 1212 murine murine JJ 1213 1216 and and CC 1217 1222 human human JJ 1223 1226 p40 p40 NN 1227 1232 genes gene NNS 1233 1239 formed form VBD 1240 1242 an an DT 1243 1252 NF-kappaB NF-kappaB NNP 1253 1260 complex complex NN 1261 1265 with with IN 1266 1273 nuclear nuclear JJ 1274 1281 extract extract NN 1282 1286 from from IN 1287 1292 Daudi Daudi NNP 1293 1298 cells cell NNS 1299 1309 stimulated stimulate VBN 1310 1312 by by IN 1313 1317 CD40 cd40 NN 1318 1326 ligation ligation NN 1326 1327 . . . 1328 1336 Moreover moreover RB 1336 1337 , , , 1338 1350 transfection transfection NN 1351 1353 of of IN 1354 1359 Daudi Daudi NNP 1360 1365 cells cell NNS 1366 1370 with with IN 1371 1374 the the DT 1375 1386 polymerized polymerized JJ 1387 1396 NF-kappaB NF-kappaB NNP 1397 1404 binding binding NN 1405 1413 sequence sequence NN 1414 1421 ligated ligate VBN 1422 1424 to to TO 1425 1426 a a DT 1427 1436 thymidine thymidine NN 1437 1459 kinase/chloramphenicol kinase/chloramphenicol NN 1460 1477 acetyltransferase acetyltransferase NN 1478 1479 ( ( ( 1479 1482 CAT CAT NNP 1482 1483 ) ) ) 1484 1492 reporter reporter NN 1493 1500 plasmid plasmid NN 1501 1508 greatly greatly RB 1509 1516 induced induce VBD 1517 1520 CAT CAT NNP 1521 1529 activity activity NN 1529 1530 , , , 1531 1534 but but CC 1535 1547 transfection transfection NN 1548 1552 with with IN 1553 1556 the the DT 1557 1568 polymerized polymerized JJ 1569 1576 mutated mutate VBN 1577 1586 NF-kappaB NF-kappaB NNP 1587 1594 binding binding NN 1595 1603 sequence sequence NN 1604 1607 did do VBD 1608 1611 not not RB 1611 1612 . . . 1613 1618 These these DT 1619 1626 results result NNS 1627 1634 suggest suggest VBP 1635 1639 that that IN 1640 1643 the the DT 1644 1653 NF-kappaB NF-kappaB NNP 1654 1661 binding binding NN 1662 1666 site site NN 1667 1674 located located JJ 1675 1681 around around IN 1682 1685 120 120 CD 1686 1688 bp bp NN 1689 1697 upstream upstream RB 1698 1700 of of IN 1701 1704 the the DT 1705 1718 transcription transcription NN 1719 1729 initiation initiation NN 1730 1734 site site NN 1735 1737 in in IN 1738 1744 murine murine JJ 1745 1748 and and CC 1749 1754 human human JJ 1755 1758 p40 p40 NN 1759 1767 promoter promoter NN 1768 1775 regions region NNS 1776 1781 could could MD 1782 1784 be be VB 1785 1794 important important JJ 1795 1798 for for IN 1799 1802 the the DT 1803 1806 p40 p40 NN 1807 1816 induction induction NN 1817 1819 by by IN 1820 1824 CD40 cd40 NN 1825 1833 ligation ligation NN 1834 1837 via via IN 1838 1848 activation activation NN 1849 1851 of of IN 1852 1861 NF-kappaB NF-kappaB NNP 1861 1862 . . .