0 11 Interleukin Interleukin NNP 12 13 ( ( ( 13 19 IL)-10 IL)-10 NNP 20 28 inhibits inhibit VBZ 29 36 nuclear nuclear JJ 37 43 factor factor NN 44 49 kappa kappa NN 50 51 B B NNP 52 53 ( ( ( 53 55 NF NF NNP 56 61 kappa kappa NN 62 63 B B NNP 63 64 ) ) ) 65 75 activation activation NN 76 78 in in IN 79 84 human human JJ 85 94 monocytes monocyte NNS 94 95 . . . 96 101 IL-10 IL-10 NNP 102 105 and and CC 106 110 IL-4 il-4 NN 111 119 suppress suppress VBP 120 128 cytokine cytokine NN 129 138 synthesis synthesis NN 139 141 by by IN 142 151 different different JJ 152 162 mechanisms mechanism NNS 162 163 . . . 165 168 Our our PRP$ 169 177 previous previous JJ 178 185 studies study NNS 186 188 in in IN 189 194 human human JJ 195 204 monocytes monocyte NNS 205 209 have have VBP 210 222 demonstrated demonstrate VBN 223 227 that that IN 228 239 interleukin interleukin NN 240 241 ( ( ( 241 247 IL)-10 IL)-10 NNP 248 256 inhibits inhibit VBZ 257 275 lipopolysaccharide lipopolysaccharide NN 276 277 ( ( ( 277 292 LPS)-stimulated lps)-stimulated JJ 293 303 production production NN 304 306 of of IN 307 319 inflammatory inflammatory JJ 320 329 cytokines cytokine NNS 329 330 , , , 331 335 IL-1 il-1 NN 336 340 beta beta NN 340 341 , , , 342 346 IL-6 IL-6 NNP 346 347 , , , 348 352 IL-8 il-8 NN 352 353 , , , 354 357 and and CC 358 363 tumor tumor NN 364 372 necrosis necrosis NN 373 379 factor factor NN 380 381 ( ( ( 381 391 TNF)-alpha TNF)-alpha NNP 392 394 by by IN 395 403 blocking block VBG 404 408 gene gene NN 409 422 transcription transcription NN 422 423 . . . 424 429 Using use VBG 430 445 electrophoretic electrophoretic JJ 446 454 mobility mobility NN 455 460 shift shift NN 461 467 assays assay NNS 468 469 ( ( ( 469 473 EMSA EMSA NNP 473 474 ) ) ) 474 475 , , , 476 478 we we PRP 479 482 now now RB 483 487 show show VBP 488 492 that that IN 492 493 , , , 494 496 in in IN 497 506 monocytes monocyte NNS 507 517 stimulated stimulate VBN 518 522 with with IN 523 526 LPS LPS NNP 527 529 or or CC 530 533 TNF TNF NNP 534 539 alpha alpha NN 539 540 , , , 541 546 IL-10 IL-10 NNP 547 555 inhibits inhibit VBZ 556 563 nuclear nuclear JJ 564 575 stimulation stimulation NN 576 578 of of IN 579 586 nuclear nuclear JJ 587 593 factor factor NN 594 599 kappa kappa NN 600 601 B B NNP 602 603 ( ( ( 603 605 NF NF NNP 606 611 kappa kappa NNP 612 613 B B NNP 613 614 ) ) ) 614 615 , , , 616 617 a a DT 618 631 transcription transcription NN 632 638 factor factor NN 639 647 involved involve VBN 648 650 in in IN 651 654 the the DT 655 665 expression expression NN 666 668 of of IN 669 681 inflammatory inflammatory JJ 682 690 cytokine cytokine NN 691 696 genes gene NNS 696 697 . . . 698 705 Several several JJ 706 711 other other JJ 712 725 transcription transcription NN 726 733 factors factor NNS 734 743 including include VBG 744 751 NF-IL-6 NF-IL-6 NNP 751 752 , , , 753 757 AP-1 AP-1 NNP 757 758 , , , 759 763 AP-2 AP-2 NNP 763 764 , , , 765 767 GR GR NNP 767 768 , , , 769 773 CREB CREB NNP 773 774 , , , 775 780 Oct-1 Oct-1 NNP 780 781 , , , 782 785 and and CC 786 790 Sp-1 Sp-1 NNP 791 794 are be VBP 795 798 not not RB 799 807 affected affect VBN 808 810 by by IN 811 816 IL-10 IL-10 NNP 816 817 . . . 818 822 This this DT 823 832 selective selective JJ 833 843 inhibition inhibition NN 844 846 by by IN 847 852 IL-10 IL-10 NNP 853 855 of of IN 856 858 NF NF NNP 859 864 kappa kappa NN 865 866 B B NNP 867 877 activation activation NN 878 884 occurs occur VBZ 885 892 rapidly rapidly RB 893 896 and and CC 897 899 in in IN 900 901 a a DT 902 916 dose-dependent dose-dependent JJ 917 923 manner manner NN 924 927 and and CC 928 938 correlates correlate VBZ 939 943 well well RB 944 948 with with IN 949 954 IL-10 il-10 NN 954 956 ’s 's POS 957 965 cytokine cytokine NN 966 975 synthesis synthesis NN 976 986 inhibitory inhibitory JJ 987 995 activity activity NN 996 998 in in IN 999 1004 terms term NNS 1005 1007 of of IN 1008 1012 both both CC 1013 1021 kinetics kinetic NNS 1022 1025 and and CC 1026 1030 dose dose NN 1031 1045 responsiveness responsiveness NN 1045 1046 . . . 1047 1058 Furthermore furthermore RB 1058 1059 , , , 1060 1069 compounds compound NNS 1070 1074 such such JJ 1075 1077 as as IN 1078 1095 tosylphenylalanyl tosylphenylalanyl NN 1096 1108 chloromethyl chloromethyl NN 1109 1115 ketone ketone NN 1116 1119 and and CC 1120 1146 pyrrolidinedithiocarbamate pyrrolidinedithiocarbamate NN 1147 1151 that that WDT 1152 1155 are be VBP 1156 1161 known know VBN 1162 1164 to to TO 1165 1176 selectively selectively RB 1177 1184 inhibit inhibit VB 1185 1187 NF NF NNP 1188 1193 kappa kappa NN 1194 1195 B B NNP 1196 1206 activation activation NN 1207 1212 block block VBP 1213 1221 cytokine cytokine NN 1222 1226 gene gene NN 1227 1240 transcription transcription NN 1241 1243 in in IN 1244 1258 LPS-stimulated lps-stimulated JJ 1259 1268 monocytes monocyte NNS 1268 1269 . . . 1270 1275 Taken take VBN 1276 1284 together together RB 1284 1285 , , , 1286 1291 these these DT 1292 1299 results result NNS 1300 1307 suggest suggest VBP 1308 1312 that that IN 1313 1323 inhibition inhibition NN 1324 1326 of of IN 1327 1329 NF NF NNP 1330 1335 kappa kappa NN 1336 1337 B B NNP 1338 1348 activation activation NN 1349 1352 may may MD 1353 1355 be be VB 1356 1358 an an DT 1359 1368 important important JJ 1369 1378 mechanism mechanism NN 1379 1382 for for IN 1383 1388 IL-10 il-10 NN 1389 1400 suppression suppression NN 1401 1403 of of IN 1404 1412 cytokine cytokine NN 1413 1417 gene gene NN 1418 1431 transcription transcription NN 1432 1434 in in IN 1435 1440 human human JJ 1441 1450 monocytes monocyte NNS 1450 1451 . . . 1452 1456 IL-4 il-4 NN 1456 1457 , , , 1458 1465 another another DT 1466 1474 cytokine cytokine NN 1475 1479 that that WDT 1480 1488 inhibits inhibit VBZ 1489 1497 cytokine cytokine NN 1498 1502 mRNA mrna NN 1503 1515 accumulation accumulation NN 1516 1518 in in IN 1519 1528 monocytes monocyte NNS 1528 1529 , , , 1530 1535 shows show VBZ 1536 1542 little little JJ 1543 1553 inhibitory inhibitory JJ 1554 1560 effect effect NN 1561 1563 on on IN 1564 1575 LPS-induced lps-induced JJ 1576 1578 NF NF NNP 1579 1584 kappa kappa NN 1585 1586 B B NNP 1587 1597 activation activation NN 1597 1598 . . . 1599 1606 Further further RB 1607 1618 examination examination NN 1619 1626 reveals reveal VBZ 1627 1631 that that IN 1631 1632 , , , 1633 1639 unlike unlike IN 1640 1645 IL-10 IL-10 NNP 1645 1646 , , , 1647 1651 IL-4 il-4 NN 1652 1660 enhances enhance VBZ 1661 1665 mRNA mrna NN 1666 1677 degradation degradation NN 1678 1681 and and CC 1682 1686 does do VBZ 1687 1690 not not RB 1691 1699 suppress suppress VB 1700 1708 cytokine cytokine NN 1709 1713 gene gene NN 1714 1727 transcription transcription NN 1727 1728 . . . 1729 1734 These these DT 1735 1739 data datum NNS 1740 1748 indicate indicate VBP 1749 1753 that that IN 1754 1759 IL-10 il-10 NN 1760 1763 and and CC 1764 1768 IL-4 il-4 NN 1769 1776 inhibit inhibit VBP 1777 1785 cytokine cytokine NN 1786 1796 production production NN 1797 1799 by by IN 1800 1809 different different JJ 1810 1820 mechanisms mechanism NNS 1820 1821 . . .