0 14 Interleukin-10 Interleukin-10 NNP 15 25 stabilizes stabilize VBZ 26 36 inhibitory inhibitory JJ 37 49 kappaB-alpha kappab-alpha NN 50 52 in in IN 53 58 human human JJ 59 68 monocytes monocyte NNS 68 69 . . . 71 85 Interleukin-10 Interleukin-10 NNP 86 87 ( ( ( 87 92 IL-10 IL-10 NNP 92 93 ) ) ) 94 102 protects protect VBZ 103 110 animals animal NNS 111 115 from from IN 116 122 lethal lethal JJ 123 134 endotoxemia endotoxemia NN 134 135 . . . 136 140 This this DT 141 151 beneficial beneficial JJ 152 158 effect effect NN 159 161 is be VBZ 162 170 mediated mediate VBN 170 171 , , , 172 174 in in IN 175 179 part part NN 179 180 , , , 181 183 by by IN 184 194 inhibition inhibition NN 195 197 of of IN 198 210 inflammatory inflammatory JJ 211 219 cytokine cytokine NN 220 230 production production NN 230 231 , , , 232 241 including include VBG 242 247 tumor tumor NN 248 256 necrosis necrosis NN 257 269 factor-alpha factor-alpha NN 270 271 ( ( ( 271 280 TNF-alpha TNF-alpha NNP 280 281 ) ) ) 281 282 . . . 283 291 Evidence evidence NN 292 300 suggests suggest VBZ 301 305 that that IN 306 311 IL-10 il-10 NN 312 315 may may MD 316 323 inhibit inhibit VB 324 334 activation activation NN 335 337 of of IN 338 341 the the DT 342 355 transcription transcription NN 356 362 factor factor NN 363 370 nuclear nuclear JJ 371 384 factor-kappaB factor-kappaB NNP 385 386 ( ( ( 386 395 NF-kappaB NF-kappaB NNP 395 396 ) ) ) 397 404 through through IN 405 407 an an DT 408 415 unknown unknown JJ 416 425 mechanism mechanism NN 425 426 . . . 427 436 NF-kappaB NF-kappaB NNP 437 447 activation activation NN 448 450 in in IN 451 459 response response NN 460 462 to to TO 463 475 inflammatory inflammatory JJ 476 483 signals signal NNS 484 486 is be VBZ 487 496 dependent dependent JJ 497 501 upon upon IN 502 513 degradation degradation NN 514 516 of of IN 517 520 its its PRP$ 521 531 associated associate VBN 532 542 inhibitory inhibitory JJ 543 550 peptide peptide NN 550 551 , , , 552 562 inhibitory inhibitory JJ 563 575 kappaB-alpha kappab-alpha NN 576 577 ( ( ( 577 590 IkappaB-alpha IkappaB-alpha NNP 590 591 ) ) ) 591 592 . . . 593 595 We we PRP 596 608 hypothesized hypothesize VBD 609 613 that that IN 614 619 IL-10 IL-10 NNP 620 628 prevents prevent VBZ 629 634 human human JJ 635 643 monocyte monocyte NN 644 653 NF-kappaB nf-kappab NN 654 664 activation activation NN 665 668 and and CC 669 678 resultant resultant JJ 679 688 TNF-alpha TNF-alpha NNP 689 699 production production NN 700 702 by by IN 703 716 stabilization stabilization NN 717 719 of of IN 720 733 IkappaB-alpha IkappaB-alpha NNP 733 734 . . . 735 738 The the DT 739 746 purpose purpose NN 747 749 of of IN 750 754 this this DT 755 760 study study NN 761 764 was be VBD 765 767 to to TO 768 777 determine determine VB 778 781 the the DT 782 788 effect effect NN 789 791 of of IN 792 797 IL-10 il-10 NN 798 800 on on IN 801 819 lipopolysaccharide lipopolysaccharide NN 820 821 ( ( ( 821 833 LPS)-induced lps)-induced JJ 834 839 human human JJ 840 848 monocyte monocyte NN 849 858 TNF-alpha TNF-alpha NNP 859 869 production production NN 869 870 , , , 871 880 NF-kappaB NF-kappaB NNP 881 891 activation activation NN 891 892 , , , 893 896 and and CC 897 910 IkappaB-alpha IkappaB-alpha NNP 911 922 degradation degradation NN 922 923 . . . 924 933 Monocytes Monocyte NNP 934 938 were be VBD 939 947 isolated isolate VBN 948 952 from from IN 953 958 human human JJ 959 965 donors donor NNS 965 966 . . . 967 972 Cells cell NNS 973 977 were be VBD 978 988 stimulated stimulate VBN 989 993 with with IN 994 1003 endotoxin endotoxin NN 1004 1005 ( ( ( 1005 1008 LPS LPS NNP 1008 1009 , , , 1010 1013 100 100 CD 1014 1019 ng/mL ng/ml NN 1019 1020 ) ) ) 1021 1025 with with IN 1026 1029 and and CC 1030 1037 without without IN 1038 1043 human human JJ 1044 1049 IL-10 il-10 NN 1050 1051 ( ( ( 1051 1053 10 10 CD 1054 1059 ng/mL ng/ml NN 1059 1060 ) ) ) 1060 1061 . . . 1062 1071 Following follow VBG 1072 1083 stimulation stimulation NN 1083 1084 , , , 1085 1094 TNF-alpha TNF-alpha NNP 1095 1098 was be VBD 1099 1107 measured measure VBN 1108 1110 in in IN 1111 1115 cell cell NN 1116 1128 supernatants supernatant NNS 1129 1131 by by IN 1132 1137 ELISA ELISA NNP 1137 1138 , , , 1139 1148 NF-kappaB NF-kappaB NNP 1149 1157 activity activity NN 1158 1160 by by IN 1161 1176 electrophoretic electrophoretic JJ 1177 1185 mobility mobility NN 1186 1191 shift shift NN 1192 1197 assay assay NN 1197 1198 , , , 1199 1202 and and CC 1203 1216 IkappaB-alpha IkappaB-alpha NNP 1217 1223 levels level NNS 1224 1226 by by IN 1227 1234 Western western JJ 1235 1239 blot blot NN 1239 1240 . . . 1241 1243 We we PRP 1244 1252 observed observe VBD 1253 1257 that that IN 1258 1263 after after IN 1264 1267 LPS LPS NNP 1268 1279 stimulation stimulation NN 1280 1282 of of IN 1283 1288 human human JJ 1289 1298 monocytes monocyte NNS 1298 1299 , , , 1300 1309 TNF-alpha TNF-alpha NNP 1310 1319 increased increase VBD 1320 1322 to to TO 1323 1331 798+/-67 798+/-67 CD 1332 1337 pg/mL pg/ml NN 1338 1339 ( ( ( 1339 1340 p p NN 1341 1342 < < JJR 1343 1347 .001 .001 CD 1348 1354 versus versus CC 1355 1362 control control NN 1362 1363 ) ) ) 1363 1364 . . . 1365 1370 IL-10 IL-10 NNP 1371 1381 attenuated attenuate VBD 1382 1396 LPS-stimulated lps-stimulated JJ 1397 1406 TNF-alpha TNF-alpha NNP 1407 1417 production production NN 1418 1419 ( ( ( 1419 1427 297+/-54 297+/-54 CD 1427 1428 ; ; : 1429 1430 p p NN 1431 1432 < < JJR 1433 1437 .001 .001 CD 1438 1444 versus versus CC 1445 1448 LPS lps NN 1449 1454 alone alone RB 1454 1455 ) ) ) 1455 1456 . . . 1457 1462 After after IN 1463 1466 LPS LPS NNP 1467 1478 stimulation stimulation NN 1479 1481 in in IN 1482 1487 human human JJ 1488 1497 monocytes monocyte NNS 1497 1498 , , , 1499 1512 IkappaB-alpha IkappaB-alpha NNP 1513 1520 protein protein NN 1521 1527 levels level NNS 1528 1537 decreased decrease VBD 1537 1538 , , , 1539 1542 and and CC 1543 1552 NF-kappaB NF-kappaB NNP 1553 1556 DNA DNA NNP 1557 1564 binding binding NN 1565 1574 increased increase VBD 1574 1575 . . . 1576 1581 IL-10 IL-10 NNP 1582 1594 pretreatment pretreatment NN 1595 1604 prevented prevent VBD 1605 1616 LPS-induced lps-induced JJ 1617 1626 decreases decrease NNS 1627 1629 in in IN 1630 1643 IkappaB-alpha IkappaB-alpha NNP 1644 1651 protein protein NN 1652 1658 levels level NNS 1659 1662 and and CC 1663 1673 attenuated attenuate VBD 1674 1683 NF-kappaB NF-kappaB NNP 1684 1687 DNA DNA NNP 1688 1695 binding binding NN 1695 1696 . . . 1697 1702 IL-10 IL-10 NNP 1703 1710 appears appear VBZ 1711 1713 to to TO 1714 1721 prevent prevent VB 1722 1732 activation activation NN 1733 1735 of of IN 1736 1745 NF-kappaB NF-kappaB NNP 1746 1748 by by IN 1749 1759 preserving preserve VBG 1760 1773 IkappaB-alpha IkappaB-alpha NNP 1774 1781 protein protein NN 1782 1788 levels level NNS 1788 1789 , , , 1790 1797 leading lead VBG 1798 1800 to to TO 1801 1802 a a DT 1803 1812 reduction reduction NN 1813 1815 in in IN 1816 1825 TNF-alpha TNF-alpha NNP 1826 1833 release release NN 1833 1834 . . .