0 5 Human human JJ 6 21 cytomegalovirus cytomegalovirus NN 22 29 binding bind VBG 30 32 to to TO 33 38 human human JJ 39 48 monocytes monocyte NNS 49 56 induces induce VBZ 57 73 immunoregulatory immunoregulatory JJ 74 78 gene gene NN 79 89 expression expression NN 89 90 . . . 92 94 To to TO 95 103 continue continue VB 104 107 our our PRP$ 108 121 investigation investigation NN 122 124 of of IN 125 128 the the DT 129 137 cellular cellular JJ 138 144 events event NNS 145 149 that that WDT 150 155 occur occur VBP 156 165 following follow VBG 166 171 human human JJ 172 175 CMV CMV NNP 176 177 ( ( ( 177 181 HCMV HCMV NNP 181 182 ) ) ) 183 192 infection infection NN 192 193 , , , 194 196 we we PRP 197 204 focused focus VBD 205 207 on on IN 208 211 the the DT 212 222 regulation regulation NN 223 225 of of IN 226 234 cellular cellular JJ 235 245 activation activation NN 246 255 following follow VBG 256 261 viral viral JJ 262 269 binding binding NN 270 272 to to TO 273 278 human human JJ 279 288 monocytes monocyte NNS 288 289 . . . 290 295 First first RB 295 296 , , , 297 299 we we PRP 300 306 showed show VBD 307 311 that that IN 312 317 viral viral JJ 318 325 binding binding NN 326 333 induced induce VBD 334 335 a a DT 336 342 number number NN 343 345 of of IN 346 362 immunoregulatory immunoregulatory JJ 363 368 genes gene NNS 369 370 ( ( ( 370 378 IL-1beta IL-1beta NNP 378 379 , , , 380 383 A20 A20 NNP 383 384 , , , 385 403 NF-kappaB-p105/p50 NF-kappaB-p105/p50 NNP 403 404 , , , 405 408 and and CC 409 421 IkappaBalpha IkappaBalpha NNP 421 422 ) ) ) 423 425 in in IN 426 437 unactivated unactivated JJ 438 447 monocytes monocyte NNS 448 451 and and CC 452 456 that that IN 457 469 neutralizing neutralize VBG 470 473 Abs ab NNS 474 476 to to TO 477 480 the the DT 481 486 major major JJ 487 491 HCMV HCMV NNP 492 505 glycoproteins glycoprotein NNS 505 506 , , , 507 509 gB gB NNP 510 511 ( ( ( 511 515 UL55 UL55 NNP 515 516 ) ) ) 517 520 and and CC 521 523 gH gH NNP 524 525 ( ( ( 525 529 UL75 UL75 NNP 529 530 ) ) ) 530 531 , , , 532 541 inhibited inhibit VBD 542 545 the the DT 546 555 induction induction NN 556 558 of of IN 559 564 these these DT 565 570 genes gene NNS 570 571 . . . 572 576 Next next RB 576 577 , , , 578 580 we we PRP 581 593 demonstrated demonstrate VBD 594 598 that that IN 599 604 these these DT 605 610 viral viral JJ 611 618 ligands ligand NNS 619 627 directly directly RB 628 640 up-regulated up-regulate VBD 641 649 monocyte monocyte NN 650 654 gene gene NN 655 665 expression expression NN 666 670 upon upon IN 671 676 their their PRP$ 677 684 binding binding NN 685 687 to to TO 688 693 their their PRP$ 694 705 appropriate appropriate JJ 706 714 cellular cellular JJ 715 724 receptors receptor NNS 724 725 . . . 726 728 We we PRP 729 733 then then RB 734 746 investigated investigate VBD 747 749 if if IN 750 754 HCMV HCMV NNP 755 762 binding binding NN 763 767 also also RB 768 776 resulted result VBD 777 779 in in IN 780 783 the the DT 784 795 translation translation NN 796 799 and and CC 800 809 secretion secretion NN 810 812 of of IN 813 822 cytokines cytokine NNS 822 823 . . . 824 827 Our our PRP$ 828 835 results result NNS 836 842 showed show VBD 843 847 that that IN 848 852 HCMV HCMV NNP 853 860 binding binding NN 861 863 to to TO 864 873 monocytes monocyte NNS 874 882 resulted result VBD 883 885 in in IN 886 889 the the DT 890 900 production production NN 901 904 and and CC 905 912 release release NN 913 915 of of IN 916 924 IL-1beta IL-1beta NNP 925 932 protein protein NN 932 933 . . . 934 941 Because because IN 942 947 these these DT 948 955 induced induce VBN 956 960 gene gene NN 961 969 products product NNS 970 974 have have VBP 975 984 NF-kappaB NF-kappaB NNP 985 990 sites site NNS 991 993 in in IN 994 999 their their PRP$ 1000 1008 promoter promoter NN 1009 1016 regions region NNS 1016 1017 , , , 1018 1020 we we PRP 1021 1025 next next RB 1026 1034 examined examine VBD 1035 1042 whether whether IN 1043 1048 there there EX 1049 1052 was be VBD 1053 1055 an an DT 1056 1069 up-regulation up-regulation NN 1070 1072 of of IN 1073 1080 nuclear nuclear JJ 1081 1090 NF-kappaB NF-kappaB NNP 1091 1097 levels level NNS 1097 1098 . . . 1099 1104 These these DT 1105 1116 experiments experiment NNS 1117 1123 showed show VBD 1124 1128 that that IN 1128 1129 , , , 1130 1132 in in IN 1133 1137 fact fact NN 1137 1138 , , , 1139 1148 NF-kappaB NF-kappaB NNP 1149 1152 was be VBD 1153 1165 translocated translocate VBN 1166 1168 to to TO 1169 1172 the the DT 1173 1180 nucleus nucleus NN 1181 1190 following follow VBG 1191 1196 viral viral JJ 1197 1204 binding binding NN 1205 1207 or or CC 1208 1216 purified purify VBN 1217 1222 viral viral JJ 1223 1229 ligand ligand NN 1230 1237 binding binding NN 1237 1238 . . . 1239 1246 Changes change NNS 1247 1249 in in IN 1250 1262 IkappaBalpha IkappaBalpha NNP 1263 1269 levels level NNS 1270 1280 correlated correlate VBD 1281 1285 with with IN 1286 1289 the the DT 1290 1297 changes change NNS 1298 1300 in in IN 1301 1310 NF-kappaB NF-kappaB NNP 1311 1324 translocation translocation NN 1324 1325 . . . 1326 1332 Lastly lastly RB 1332 1333 , , , 1334 1336 we we PRP 1337 1349 demonstrated demonstrate VBD 1350 1354 that that IN 1355 1358 p38 p38 NN 1359 1365 kinase kinase NNP 1366 1374 activity activity NN 1375 1381 played play VBD 1382 1383 a a DT 1384 1391 central central JJ 1392 1396 role role NN 1397 1399 in in IN 1400 1408 IL-1beta IL-1beta NNP 1409 1419 production production NN 1420 1423 and and CC 1424 1428 that that IN 1429 1431 it it PRP 1432 1435 was be VBD 1436 1443 rapidly rapidly RB 1444 1456 up-regulated up-regulate VBN 1457 1466 following follow VBG 1467 1476 infection infection NN 1476 1477 . . . 1478 1483 These these DT 1484 1491 results result NNS 1492 1499 support support VBP 1500 1503 our our PRP$ 1504 1514 hypothesis hypothesis NN 1515 1519 that that IN 1520 1524 HCMV HCMV NNP 1525 1534 initiates initiate VBZ 1535 1536 a a DT 1537 1543 signal signal NN 1544 1556 transduction transduction NN 1557 1564 pathway pathway NN 1565 1569 that that WDT 1570 1575 leads lead VBZ 1576 1578 to to TO 1579 1587 monocyte monocyte NN 1588 1598 activation activation NN 1599 1602 and and CC 1603 1612 pinpoints pinpoint VBZ 1613 1614 a a DT 1615 1624 potential potential JJ 1625 1634 mechanism mechanism NN 1635 1642 whereby whereby WRB 1643 1647 HCMV HCMV NNP 1648 1657 infection infection NN 1658 1660 of of IN 1661 1670 monocytes monocyte NNS 1671 1674 can can MD 1675 1681 result result VB 1682 1684 in in IN 1685 1693 profound profound JJ 1694 1706 pathogenesis pathogenesis NN 1706 1707 , , , 1708 1718 especially especially RB 1719 1721 in in IN 1722 1729 chronic chronic JJ 1730 1747 inflammatory-type inflammatory-type JJ 1748 1758 conditions condition NNS 1758 1759 . . .