0 14 Interleukin-10 Interleukin-10 NNP 15 23 inhibits inhibit VBZ 24 34 expression expression NN 35 37 of of IN 38 42 both both CC 43 53 interferon interferon NN 54 60 alpha- alpha- NN 61 64 and and CC 65 75 interferon interferon NN 76 82 gamma- gamma- NN 83 90 induced induce VBD 91 96 genes gene NNS 97 99 by by IN 100 111 suppressing suppress VBG 112 120 tyrosine tyrosine NN 121 136 phosphorylation phosphorylation NN 137 139 of of IN 140 145 STAT1 STAT1 NNP 145 146 . . . 148 162 Interleukin-10 Interleukin-10 NNP 163 164 ( ( ( 164 169 IL-10 IL-10 NNP 169 170 ) ) ) 171 176 helps help VBZ 177 185 maintain maintain VB 186 195 polarized polarize VBN 196 204 T-helper T-helper NNP 205 210 cells cell NNS 211 213 in in IN 214 215 a a DT 216 224 T-helper T-helper NNP 225 235 lymphocyte lymphocyte NN 236 237 2 2 CD 238 239 ( ( ( 239 242 Th2 th2 NN 242 243 ) ) ) 244 253 phenotype phenotype NN 253 254 . . . 255 259 Part part NN 260 262 of of IN 263 267 this this DT 268 275 process process NN 276 284 involves involve VBZ 285 288 the the DT 289 299 prevention prevention NN 300 302 of of IN 303 306 the the DT 307 318 development development NN 319 321 of of IN 322 325 Th1 th1 NN 326 331 cells cell NNS 331 332 , , , 333 338 which which WDT 339 342 are be VBP 343 344 a a DT 345 352 primary primary JJ 353 359 source source NN 360 362 of of IN 363 373 interferon interferon NN 374 379 gamma gamma NN 380 381 ( ( ( 381 389 IFNgamma IFNgamma NNP 389 390 ) ) ) 390 391 , , , 392 393 a a DT 394 400 potent potent JJ 401 410 activator activator NN 411 413 of of IN 414 423 monocytes monocyte NNS 424 427 and and CC 428 430 an an DT 431 440 inhibitor inhibitor NN 441 443 of of IN 444 447 Th2 th2 NN 448 461 proliferation proliferation NN 461 462 . . . 463 470 Because because IN 471 480 monocytes monocyte NNS 481 484 and and CC 485 496 macrophages macrophage NNS 497 500 are be VBP 501 510 important important JJ 511 520 mediators mediator NNS 521 523 of of IN 524 532 Th1-type th1-type JJ 533 542 responses response NNS 542 543 , , , 544 548 such such JJ 549 551 as as IN 552 564 delayed-type delayed-type JJ 565 581 hypersensitivity hypersensitivity NN 581 582 , , , 583 585 we we PRP 586 592 sought seek VBD 593 595 to to TO 596 605 determine determine VB 606 608 if if IN 609 614 IL-10 IL-10 NNP 615 620 could could MD 621 629 directly directly RB 630 637 mediate mediate VB 638 648 inhibition inhibition NN 649 651 of of IN 652 661 IFNgamma- IFNgamma- NNP 662 665 and and CC 666 682 IFNalpha-induced ifnalpha-induced JJ 683 687 gene gene NN 688 698 expression expression NN 699 701 in in IN 702 707 these these DT 708 713 cells cell NNS 713 714 . . . 715 721 Highly highly RB 722 730 purified purify VBN 731 740 monocytes monocyte NNS 741 745 were be VBD 746 755 incubated incubate VBN 756 760 with with IN 761 766 IL-10 il-10 NN 767 770 for for IN 771 773 60 60 CD 774 776 to to TO 777 779 90 90 CD 780 787 minutes minute NNS 788 794 before before IN 795 798 the the DT 799 807 addition addition NN 808 810 of of IN 811 819 IFNgamma IFNgamma NNP 820 822 or or CC 823 831 IFNalpha IFNalpha NNP 831 832 . . . 833 838 IL-10 IL-10 NNP 839 852 preincubation preincubation NN 853 861 resulted result VBD 862 864 in in IN 865 868 the the DT 869 879 inhibition inhibition NN 880 882 of of IN 883 887 gene gene NN 888 898 expression expression NN 899 902 for for IN 903 910 several several JJ 911 922 IFN-induced ifn-induced JJ 923 928 genes gene NNS 928 929 , , , 930 934 such such JJ 935 937 as as IN 938 943 IP-10 IP-10 NNP 943 944 , , , 945 950 ISG54 ISG54 NNP 950 951 , , , 952 955 and and CC 956 969 intercellular intercellular JJ 970 978 adhesion adhesion NN 979 989 molecule-1 molecule-1 NN 989 990 . . . 991 994 The the DT 995 1004 reduction reduction NN 1005 1007 in in IN 1008 1012 gene gene NN 1013 1023 expression expression NN 1024 1032 resulted result VBD 1033 1037 from from IN 1038 1041 the the DT 1042 1049 ability ability NN 1050 1052 of of IN 1053 1058 IL-10 IL-10 NNP 1059 1061 to to TO 1062 1070 suppress suppress VB 1071 1082 IFN-induced ifn-induced JJ 1083 1091 assembly assembly NN 1092 1094 of of IN 1095 1101 signal signal NN 1102 1112 transducer transducer NN 1113 1116 and and CC 1117 1126 activator activator NN 1127 1129 of of IN 1130 1143 transcription transcription NN 1144 1145 ( ( ( 1145 1149 STAT STAT NNP 1149 1150 ) ) ) 1151 1158 factors factor NNS 1159 1161 to to TO 1162 1170 specific specific JJ 1171 1179 promoter promoter NN 1180 1186 motifs motif NNS 1187 1189 on on IN 1190 1199 IFNalpha- ifnalpha- NN 1200 1203 and and CC 1204 1222 IFNgamma-inducible ifngamma-inducible JJ 1223 1228 genes gene NNS 1228 1229 . . . 1230 1234 This this DT 1235 1238 was be VBD 1239 1251 accomplished accomplish VBN 1252 1254 by by IN 1255 1265 preventing prevent VBG 1266 1269 the the DT 1270 1281 IFN-induced ifn-induced JJ 1282 1290 tyrosine tyrosine NN 1291 1306 phosphorylation phosphorylation NN 1307 1309 of of IN 1310 1315 STAT1 STAT1 NNP 1315 1316 , , , 1317 1318 a a DT 1319 1328 component component NN 1329 1331 of of IN 1332 1336 both both CC 1337 1346 IFNalpha- IFNalpha- NNP 1347 1350 and and CC 1351 1367 IFNgamma-induced ifngamma-induced JJ 1368 1371 DNA DNA NNP 1372 1379 binding binding NN 1380 1389 complexes complex NNS 1389 1390 . . . 1391 1400 Therefore therefore RB 1400 1401 , , , 1402 1407 IL-10 IL-10 NNP 1408 1411 can can MD 1412 1420 directly directly RB 1421 1428 inhibit inhibit VB 1429 1443 STAT-dependent stat-dependent JJ 1444 1449 early early JJ 1450 1458 response response NN 1459 1463 gene gene NN 1464 1474 expression expression NN 1475 1482 induced induce VBN 1483 1485 by by IN 1486 1490 both both CC 1491 1499 IFNalpha IFNalpha NNP 1500 1503 and and CC 1504 1512 IFNgamma IFNgamma NNP 1513 1515 in in IN 1516 1525 monocytes monocyte NNS 1526 1528 by by IN 1529 1540 suppressing suppress VBG 1541 1544 the the DT 1545 1553 tyrosine tyrosine NN 1554 1569 phosphorylation phosphorylation NN 1570 1572 of of IN 1573 1578 STAT1 STAT1 NNP 1578 1579 . . . 1580 1584 This this DT 1585 1588 may may MD 1589 1594 occur occur VB 1595 1602 through through IN 1603 1606 the the DT 1607 1614 ability ability NN 1615 1617 of of IN 1618 1623 IL-10 IL-10 NNP 1624 1626 to to TO 1627 1633 induce induce VB 1634 1644 expression expression NN 1645 1647 of of IN 1648 1651 the the DT 1652 1656 gene gene NN 1656 1657 , , , 1658 1668 suppressor suppressor NN 1669 1671 of of IN 1672 1680 cytokine cytokine NN 1681 1690 signaling signaling NN 1691 1692 3 3 CD 1693 1694 ( ( ( 1694 1699 SOCS3 socs3 NN 1699 1700 ) ) ) 1700 1701 . . .