0 13 Prostaglandin prostaglandin NN 14 16 E2 E2 NNP 17 29 Up-regulates up-regulate VBZ 30 35 HIV-1 HIV-1 NNP 36 40 long long JJ 41 49 terminal terminal JJ 50 63 repeat-driven repeat-driven JJ 64 68 gene gene NN 69 77 activity activity NN 78 80 in in IN 81 82 T t NN 83 88 cells cell NNS 89 92 via via IN 93 112 NF-kappaB-dependent nf-kappab-dependent JJ 113 116 and and CC 117 129 -independent -independent JJ 130 139 signaling signaling NN 140 148 pathways pathway NNS 148 149 . . . 151 162 Replication Replication NNP 163 165 of of IN 166 171 human human JJ 172 188 immunodeficiency immunodeficiency NN 189 194 virus virus NN 195 201 type-1 type-1 NN 202 203 ( ( ( 203 208 HIV-1 HIV-1 NNP 208 209 ) ) ) 210 212 is be VBZ 213 219 highly highly RB 220 229 dependent dependent JJ 230 232 on on IN 233 236 the the DT 237 242 state state NN 243 245 of of IN 246 256 activation activation NN 257 259 of of IN 260 263 the the DT 264 272 infected infected JJ 273 278 cells cell NNS 279 282 and and CC 283 285 is be VBZ 286 295 modulated modulate VBN 296 298 by by IN 299 311 interactions interaction NNS 312 319 between between IN 320 325 viral viral JJ 326 329 and and CC 330 334 host host NN 335 343 cellular cellular JJ 344 351 factors factor NNS 351 352 . . . 353 366 Prostaglandin prostaglandin NN 367 369 E2 e2 NN 370 371 ( ( ( 371 375 PGE2 PGE2 NNP 375 376 ) ) ) 376 377 , , , 378 379 a a DT 380 391 pleiotropic pleiotropic JJ 392 408 immunomodulatory immunomodulatory JJ 409 417 molecule molecule NN 417 418 , , , 419 421 is be VBZ 422 430 observed observe VBN 431 433 at at IN 434 442 elevated elevated JJ 443 449 levels level NNS 450 456 during during IN 457 462 HIV-1 HIV-1 NNP 463 472 infection infection NN 473 475 as as RB 476 480 well well RB 481 483 as as IN 484 490 during during IN 491 494 the the DT 495 501 course course NN 502 504 of of IN 505 510 other other JJ 511 521 pathogenic pathogenic JJ 522 532 infections infection NNS 532 533 . . . 534 536 In in IN 537 540 1G5 1g5 NN 540 541 , , , 542 543 a a DT 544 558 Jurkat-derived jurkat-derived JJ 559 560 T t NN 561 565 cell cell NN 566 570 line line NN 571 577 stably stably RB 578 589 transfected transfecte VBN 590 594 with with IN 595 596 a a DT 597 607 luciferase luciferase NN 608 612 gene gene NN 613 619 driven drive VBN 620 622 by by IN 623 628 HIV-1 HIV-1 NNP 629 633 long long JJ 634 642 terminal terminal JJ 643 649 repeat repeat NN 650 651 ( ( ( 651 654 LTR LTR NNP 654 655 ) ) ) 655 656 , , , 657 659 we we PRP 660 665 found find VBD 666 670 that that IN 671 675 PGE2 pge2 NN 676 684 markedly markedly RB 685 693 enhanced enhance VBD 694 699 HIV-1 HIV-1 NNP 700 712 LTR-mediated ltr-mediated JJ 713 721 reporter reporter NN 722 726 gene gene NN 727 735 activity activity NN 735 736 . . . 737 748 Experiments experiment NNS 749 753 have have VBP 754 758 been be VBN 759 768 conducted conduct VBN 769 771 to to TO 772 780 identify identify VB 781 787 second second JJ 788 798 messengers messenger NNS 799 807 involved involve VBN 808 810 in in IN 811 815 this this DT 816 830 PGE2-dependent pge2-dependent JJ 831 844 up-regulating up-regulating JJ 845 851 effect effect NN 852 854 on on IN 855 858 the the DT 859 869 regulatory regulatory JJ 870 877 element element NN 878 880 of of IN 881 886 HIV-1 HIV-1 NNP 886 887 . . . 888 890 In in IN 891 895 this this DT 896 901 study study NN 901 902 , , , 903 905 we we PRP 906 913 present present VBP 914 922 evidence evidence NN 923 933 indicating indicate VBG 934 938 that that IN 939 945 signal signal NN 946 958 transduction transduction NN 959 967 pathways pathway NNS 968 975 induced induce VBN 976 978 by by IN 979 983 PGE2 pge2 NN 984 995 necessitate necessitate VBP 996 999 the the DT 1000 1013 participation participation NN 1014 1016 of of IN 1017 1023 cyclic cyclic JJ 1024 1027 AMP AMP NNP 1027 1028 , , , 1029 1036 protein protein NN 1037 1043 kinase kinase NNP 1044 1045 A A NNP 1045 1046 , , , 1047 1050 and and CC 1051 1055 Ca2+ Ca2+ NNP 1055 1056 . . . 1057 1068 Experiments experiment NNS 1069 1078 conducted conduct VBN 1079 1083 with with IN 1084 1093 different different JJ 1094 1099 HIV-1 HIV-1 NNP 1100 1109 LTR-based ltr-based JJ 1110 1117 vectors vector NNS 1118 1127 suggested suggest VBD 1128 1132 that that IN 1133 1146 PGE2-mediated pge2-mediated JJ 1147 1157 activation activation NN 1158 1164 effect effect NN 1165 1167 on on IN 1168 1173 HIV-1 HIV-1 NNP 1174 1187 transcription transcription NN 1188 1191 was be VBD 1192 1202 transduced transduce VBN 1203 1206 via via IN 1207 1211 both both CC 1212 1231 NF-kappaB-dependent nf-kappab-dependent JJ 1232 1235 and and CC 1236 1248 -independent -independent JJ 1249 1258 signaling signaling NN 1259 1267 pathways pathway NNS 1267 1268 . . . 1269 1272 The the DT 1273 1284 involvement involvement NN 1285 1287 of of IN 1288 1297 NF-kappaB NF-kappaB NNP 1298 1300 in in IN 1301 1304 the the DT 1305 1319 PGE2-dependent pge2-dependent JJ 1320 1330 activating activate VBG 1331 1337 effect effect NN 1338 1340 on on IN 1341 1346 HIV-1 HIV-1 NNP 1347 1360 transcription transcription NN 1361 1364 was be VBD 1365 1372 further further RB 1373 1382 confirmed confirm VBN 1383 1388 using use VBG 1389 1390 a a DT 1391 1407 kappaB-regulated kappab-regulated JJ 1408 1418 luciferase luciferase NN 1419 1427 encoding encoding NN 1428 1434 vector vector NN 1435 1438 and and CC 1439 1441 by by IN 1442 1457 electrophoretic electrophoretic JJ 1458 1466 mobility mobility NN 1467 1472 shift shift NN 1473 1479 assays assay NNS 1479 1480 . . . 1481 1488 Results result NNS 1489 1493 from from IN 1494 1502 Northern northern NN 1503 1507 blot blot NN 1508 1511 and and CC 1512 1516 flow flow NN 1517 1527 cytometric cytometric JJ 1528 1536 analyses analysis NNS 1536 1537 , , , 1538 1540 as as RB 1541 1545 well well RB 1546 1548 as as IN 1549 1552 the the DT 1553 1556 use use NN 1557 1559 of of IN 1560 1561 a a DT 1562 1571 selective selective JJ 1572 1582 antagonist antagonist NN 1583 1592 indicated indicate VBD 1593 1597 that that IN 1598 1602 PGE2 pge2 NN 1603 1613 modulation modulation NN 1614 1616 of of IN 1617 1622 HIV-1 HIV-1 NNP 1623 1633 LTR-driven ltr-driven JJ 1634 1642 reporter reporter NN 1643 1647 gene gene NN 1648 1656 activity activity NN 1657 1659 in in IN 1660 1667 studied study VBN 1668 1669 T t NN 1670 1678 lymphoid lymphoid JJ 1679 1684 cells cell NNS 1685 1687 is be VBZ 1688 1698 transduced transduce VBN 1699 1702 via via IN 1703 1706 the the DT 1707 1710 EP4 ep4 NN 1711 1719 receptor receptor NN 1720 1727 subtype subtype NN 1727 1728 . . . 1729 1734 These these DT 1735 1742 results result NNS 1743 1750 suggest suggest VBP 1751 1755 that that IN 1756 1765 secretion secretion NN 1766 1768 of of IN 1769 1773 PGE2 pge2 NN 1774 1776 by by IN 1777 1788 macrophages macrophage NNS 1789 1791 in in IN 1792 1800 response response NN 1801 1803 to to TO 1804 1813 infection infection NN 1814 1816 or or CC 1817 1829 inflammatory inflammatory JJ 1830 1840 activators activator NNS 1841 1846 could could MD 1847 1853 induce induce VB 1854 1863 signaling signaling NN 1864 1870 events event NNS 1871 1880 resulting result VBG 1881 1883 in in IN 1884 1894 activation activation NN 1895 1897 of of IN 1898 1906 proviral proviral JJ 1907 1910 DNA dna NN 1911 1918 present present JJ 1919 1923 into into IN 1924 1925 T t NN 1926 1931 cells cell NNS 1932 1940 latently latently RB 1941 1949 infected infect VBN 1950 1954 with with IN 1955 1960 HIV-1 HIV-1 NNP 1960 1961 . . .