0 15 Cytomegalovirus Cytomegalovirus NNP 16 25 immediate immediate JJ 26 31 early early JJ 32 37 genes gene NNS 38 48 upregulate upregulate VBP 49 62 interleukin-6 interleukin-6 NN 63 67 gene gene NN 68 78 expression expression NN 78 79 . . . 81 91 BACKGROUND background NN 91 92 : : : 93 96 The the DT 97 106 immediate immediate JJ 107 112 early early JJ 113 118 genes gene NNS 119 120 ( ( ( 120 122 IE IE NNP 122 123 ) ) ) 124 126 of of IN 127 132 human human JJ 133 148 cytomegalovirus cytomegalovirus NN 149 150 ( ( ( 150 153 CMV CMV NNP 153 154 ) ) ) 155 158 can can MD 159 161 be be VB 162 171 expressed express VBN 172 174 in in IN 175 184 monocytic monocytic JJ 185 190 cells cell NNS 191 194 and and CC 195 198 are be VBP 199 204 known know VBN 205 207 to to TO 208 216 regulate regulate VB 217 222 viral viral JJ 223 226 and and CC 227 235 cellular cellular JJ 236 241 genes gene NNS 241 242 . . . 243 256 Interleukin-6 Interleukin-6 NNP 257 258 ( ( ( 258 262 IL-6 IL-6 NNP 262 263 ) ) ) 264 269 plays play VBZ 270 271 a a DT 272 279 central central JJ 280 284 role role NN 285 287 in in IN 288 296 numerous numerous JJ 297 309 inflammatory inflammatory JJ 310 313 and and CC 314 320 immune immune JJ 321 330 processes process NNS 330 331 . . . 332 345 Interleukin-6 Interleukin-6 NNP 346 352 levels level NNS 353 356 are be VBP 357 366 increased increase VBN 367 369 in in IN 370 374 lung lung NN 375 385 transplant transplant NN 386 394 patients patient NNS 395 405 clinically clinically RB 406 415 diagnosed diagnose VBN 416 420 with with IN 421 424 CMV CMV NNP 425 436 pneumonitis pneumonitis NN 436 437 . . . 438 441 The the DT 442 452 regulation regulation NN 453 455 of of IN 456 460 IL-6 IL-6 NNP 461 463 is be VBZ 464 473 dependent dependent JJ 474 476 on on IN 477 484 various various JJ 485 492 stimuli stimulus NNS 493 497 that that WDT 498 505 include include VBP 506 524 lipopolysaccharide lipopolysaccharide NN 525 526 ( ( ( 526 529 LPS LPS NNP 529 530 ) ) ) 530 531 , , , 532 539 viruses virus NNS 539 540 , , , 541 544 and and CC 545 550 other other JJ 551 560 cytokines cytokine NNS 560 561 . . . 562 567 These these DT 568 575 studies study NNS 576 584 examined examine VBD 585 588 the the DT 589 596 ability ability NN 597 599 of of IN 600 603 CMV CMV NNP 604 606 IE IE NNP 607 611 gene gene NN 612 620 products product NNS 621 623 to to TO 624 632 modulate modulate VB 633 637 IL-6 IL-6 NNP 638 648 production production NN 648 649 . . . 650 657 METHODS methods NNS 657 658 : : : 659 664 THP-1 thp-1 NN 665 670 cells cell NNS 670 671 , , , 672 673 a a DT 674 683 monocytic monocytic JJ 684 688 cell cell NN 689 693 line line NN 693 694 , , , 695 699 were be VBD 700 711 transfected transfecte VBN 712 716 with with IN 717 720 the the DT 721 724 CMV CMV NNP 725 727 IE IE NNP 728 733 genes gene NNS 733 734 . . . 735 748 Interleukin-6 Interleukin-6 NNP 749 756 protein protein NN 757 760 and and CC 761 765 IL-6 IL-6 NNP 766 770 mRNA mRNA NNP 771 775 were be VBD 776 784 measured measure VBN 785 787 in in IN 788 795 control control NN 796 799 and and CC 800 803 CMV CMV NNP 804 813 immediate immediate JJ 814 819 early early JJ 820 831 transfected transfecte VBN 832 837 cells cell NNS 837 838 . . . 839 853 Cotransfection Cotransfection NNP 854 856 of of IN 857 860 CMV CMV NNP 861 863 IE IE NNP 864 869 genes gene NNS 870 873 and and CC 874 878 IL-6 il-6 NN 879 894 chloramphenicol chloramphenicol NN 895 901 acetyl acetyl NN 902 913 transferase transferase NN 914 915 ( ( ( 915 918 CAT CAT NNP 918 919 ) ) ) 920 922 or or CC 923 927 IL-6 IL-6 NNP 928 938 luciferase luciferase NN 939 949 constructs construct NNS 950 954 were be VBD 955 959 used use VBN 960 962 to to TO 963 968 study study VB 969 973 IL-6 il-6 NN 974 982 promoter promoter NN 983 991 activity activity NN 991 992 . . . 993 1000 RESULTS results NNS 1000 1001 : : : 1002 1015 Interleukin-6 interleukin-6 NN 1016 1023 protein protein NN 1024 1027 and and CC 1028 1032 mRNA mrna NN 1033 1043 production production NN 1044 1048 were be VBD 1049 1062 significantly significantly RB 1063 1072 increased increase VBN 1073 1075 in in IN 1076 1081 cells cell NNS 1082 1093 transfected transfecte VBN 1094 1098 with with IN 1099 1102 the the DT 1103 1106 CMV CMV NNP 1107 1109 IE IE NNP 1110 1115 genes gene NNS 1116 1119 and and CC 1120 1130 stimulated stimulate VBN 1131 1135 with with IN 1136 1139 LPS lps NN 1140 1148 compared compare VBN 1149 1151 to to TO 1152 1166 LPS-stimulated lps-stimulated JJ 1167 1174 control control NN 1175 1180 cells cell NNS 1180 1181 . . . 1182 1197 Cytomegalovirus Cytomegalovirus NNP 1198 1200 IE IE NNP 1201 1205 gene gene NN 1206 1214 products product NNS 1215 1228 significantly significantly RB 1229 1237 enhanced enhance VBD 1238 1241 LPS LPS NNP 1242 1253 stimulation stimulation NN 1254 1256 of of IN 1257 1261 IL-6 IL-6 NNP 1262 1270 promoter promoter NN 1271 1279 activity activity NN 1280 1282 in in IN 1283 1287 both both CC 1288 1292 IL-6 IL-6 NNP 1293 1296 CAT CAT NNP 1297 1300 and and CC 1301 1305 IL-6 IL-6 NNP 1306 1316 luciferase luciferase NN 1317 1323 assays assay NNS 1323 1324 . . . 1325 1326 A a DT 1327 1335 deletion deletion NN 1336 1345 construct construct NN 1346 1350 that that WDT 1351 1359 contains contain VBZ 1360 1361 a a DT 1362 1370 NF-kappa NF-kappa NNP 1371 1372 B B NNP 1373 1377 site site NN 1378 1381 but but CC 1382 1384 is be VBZ 1385 1392 missing miss VBG 1393 1396 the the DT 1397 1405 multiple multiple JJ 1406 1414 response response NN 1415 1421 region region NN 1422 1434 demonstrated demonstrate VBD 1435 1436 a a DT 1437 1446 continued continued JJ 1447 1455 increase increase NN 1456 1458 in in IN 1459 1463 IL-6 IL-6 NNP 1464 1474 luciferase luciferase NN 1475 1483 activity activity NN 1484 1486 in in IN 1487 1501 LPS-stimulated lps-stimulated JJ 1502 1505 CMV CMV NNP 1506 1517 transfected transfected JJ 1518 1523 cells cell NNS 1523 1524 . . . 1525 1535 CONCLUSION conclusion NN 1535 1536 : : : 1537 1552 Cytomegalovirus Cytomegalovirus NNP 1553 1562 immediate immediate JJ 1563 1568 early early JJ 1569 1573 gene gene NN 1574 1582 products product NNS 1583 1596 significantly significantly RB 1597 1605 enhanced enhance VBD 1606 1616 expression expression NN 1617 1619 of of IN 1620 1624 IL-6 il-6 NN 1625 1627 in in IN 1628 1642 LPS-stimulated lps-stimulated JJ 1643 1648 cells cell NNS 1648 1649 . . . 1650 1653 The the DT 1654 1662 increase increase NN 1663 1665 in in IN 1666 1670 IL-6 IL-6 NNP 1671 1681 luciferase luciferase NN 1682 1690 activity activity NN 1691 1697 occurs occur VBZ 1698 1700 in in IN 1701 1704 the the DT 1705 1712 absence absence NN 1713 1715 of of IN 1716 1719 the the DT 1720 1728 multiple multiple JJ 1729 1737 response response NN 1738 1744 region region NN 1744 1745 , , , 1746 1749 the the DT 1750 1754 area area NN 1755 1757 of of IN 1758 1761 the the DT 1762 1766 IL-6 il-6 NN 1767 1775 promoter promoter NN 1776 1786 responsive responsive JJ 1787 1789 to to TO 1790 1794 IL-1 il-1 NN 1794 1795 , , , 1796 1799 TNF TNF NNP 1800 1805 alpha alpha NN 1805 1806 , , , 1807 1813 cyclic cyclic JJ 1814 1817 amp amp NN 1817 1818 , , , 1819 1822 and and CC 1823 1830 phorbol phorbol NN 1831 1843 12-myristate 12-myristate NN 1844 1854 13-acetate 13-acetate NN 1854 1855 . . . 1856 1859 The the DT 1860 1867 ability ability NN 1868 1870 of of IN 1871 1874 CMV CMV NNP 1875 1877 IE IE NNP 1878 1882 gene gene NN 1883 1891 products product NNS 1892 1894 to to TO 1895 1902 enhance enhance VB 1903 1907 IL-6 il-6 NN 1908 1918 production production NN 1919 1922 may may MD 1923 1927 play play VB 1928 1930 an an DT 1931 1940 important important JJ 1941 1945 role role NN 1946 1948 in in IN 1949 1955 immune immune JJ 1956 1968 inflammatory inflammatory JJ 1969 1975 states state NNS 1976 1986 associated associate VBN 1987 1991 with with IN 1992 1995 CMV CMV NNP 1996 2005 infection infection NN 2005 2006 . . .