0 8 Elevated elevated JJ 9 15 cyclic cyclic JJ 16 19 AMP amp NN 20 28 inhibits inhibit VBZ 29 47 NF-kappaB-mediated nf-kappab-mediated JJ 48 61 transcription transcription NN 62 64 in in IN 65 70 human human JJ 71 80 monocytic monocytic JJ 81 86 cells cell NNS 87 90 and and CC 91 102 endothelial endothelial JJ 103 108 cells cell NNS 108 109 . . . 111 114 The the DT 115 128 NF-kappaB/Rel NF-kappaB/Rel NNP 129 135 family family NN 136 138 of of IN 139 152 transcription transcription NN 153 160 factors factor NNS 161 170 regulates regulate VBZ 171 174 the the DT 175 184 inducible inducible JJ 185 195 expression expression NN 196 198 of of IN 199 203 many many JJ 204 209 genes gene NNS 210 212 in in IN 213 222 activated activate VBN 223 228 human human JJ 229 238 monocytes monocyte NNS 239 242 and and CC 243 254 endothelial endothelial JJ 255 260 cells cell NNS 260 261 . . . 262 264 In in IN 265 269 this this DT 270 275 study study NN 275 276 , , , 277 279 we we PRP 280 288 examined examine VBD 289 292 the the DT 293 302 molecular molecular JJ 303 312 mechanism mechanism NN 313 315 by by IN 316 321 which which WDT 322 328 agents agent NNS 329 333 that that WDT 334 341 elevate elevate VBP 342 355 intracellular intracellular JJ 356 360 cAMP camp NN 361 368 inhibit inhibit VBP 369 372 the the DT 373 383 expression expression NN 384 386 of of IN 387 390 the the DT 391 396 tumor tumor NN 397 405 necrosis necrosis NN 406 412 factor factor NN 413 418 alpha alpha NN 419 420 ( ( ( 420 428 TNFalpha TNFalpha NNP 428 429 ) ) ) 429 430 , , , 431 437 tissue tissue NN 438 444 factor factor NN 444 445 , , , 446 457 endothelial endothelial JJ 458 467 leukocyte leukocyte NN 468 476 adhesion adhesion NN 477 487 molecule-1 molecule-1 NN 487 488 , , , 489 492 and and CC 493 501 vascular vascular JJ 502 506 cell cell NN 507 515 adhesion adhesion NN 516 526 molecule-1 molecule-1 NN 527 532 genes gene NNS 532 533 . . . 534 538 Both both CC 539 548 forskolin forskolin NN 549 552 and and CC 553 562 dibutyryl dibutyryl NN 563 567 cAMP camp NN 567 568 , , , 569 574 which which WDT 575 582 elevate elevate VBP 583 596 intracellular intracellular JJ 597 601 cAMP camp NN 602 604 by by IN 605 616 independent independent JJ 617 627 mechanisms mechanism NNS 627 628 , , , 629 638 inhibited inhibit VBD 639 647 TNFalpha TNFalpha NNP 648 651 and and CC 652 658 tissue tissue NN 659 665 factor factor NN 666 676 expression expression NN 677 679 at at IN 680 683 the the DT 684 689 level level NN 690 692 of of IN 693 706 transcription transcription NN 706 707 . . . 708 717 Induction Induction NNP 718 720 of of IN 721 740 NF-kappaB-dependent nf-kappab-dependent JJ 741 745 gene gene NN 746 756 expression expression NN 757 759 in in IN 760 771 transiently transiently RB 772 783 transfected transfecte VBN 784 789 human human JJ 790 799 monocytic monocytic JJ 800 805 THP-1 thp-1 NN 806 811 cells cell NNS 812 815 and and CC 816 821 human human JJ 822 831 umbilical umbilical JJ 832 836 vein vein NN 837 848 endothelial endothelial JJ 849 854 cells cell NNS 855 858 was be VBD 859 868 inhibited inhibit VBN 869 871 by by IN 872 880 elevated elevated JJ 881 885 cAMP camp NN 886 889 and and CC 890 892 by by IN 893 907 overexpression overexpression NN 908 910 of of IN 911 914 the the DT 915 924 catalytic catalytic JJ 925 932 subunit subunit NN 933 935 of of IN 936 943 protein protein NN 944 950 kinase kinase NNP 951 952 A A NNP 953 954 ( ( ( 954 957 PKA PKA NNP 957 958 ) ) ) 958 959 . . . 960 968 Elevated elevated JJ 969 973 cAMP camp NN 974 977 did do VBD 978 981 not not RB 982 989 prevent prevent VB 990 997 nuclear nuclear JJ 998 1011 translocation translocation NN 1012 1014 of of IN 1015 1022 p50/p65 p50/p65 NN 1023 1026 and and CC 1027 1036 c-Rel/p65 c-rel/p65 NN 1037 1049 heterodimers heterodimer NNS 1049 1050 , , , 1051 1059 decrease decrease VB 1060 1067 nuclear nuclear JJ 1068 1081 translocation translocation NN 1082 1084 of of IN 1085 1088 p65 p65 NN 1088 1089 , , , 1090 1092 or or CC 1093 1106 significantly significantly RB 1107 1113 modify modify VB 1114 1130 TNFalpha-induced tnfalpha-induced JJ 1131 1146 phosphorylation phosphorylation NN 1147 1149 of of IN 1150 1153 p65 p65 NN 1153 1154 . . . 1155 1165 Functional functional JJ 1166 1173 studies study NNS 1174 1186 demonstrated demonstrate VBD 1187 1191 that that IN 1192 1207 transcriptional transcriptional JJ 1208 1218 activation activation NN 1219 1221 of of IN 1222 1223 a a DT 1224 1231 plasmid plasmid NN 1232 1242 containing contain VBG 1243 1255 multimerized multimerized JJ 1256 1262 kappaB kappab NN 1263 1268 sites site NNS 1269 1271 by by IN 1272 1275 p65 p65 NN 1276 1279 was be VBD 1280 1289 inhibited inhibit VBN 1290 1292 by by IN 1293 1299 agents agent NNS 1300 1304 that that WDT 1305 1312 elevate elevate VBP 1313 1317 cAMP camp NN 1318 1321 and and CC 1322 1324 by by IN 1325 1339 overexpression overexpression NN 1340 1342 of of IN 1343 1346 the the DT 1347 1356 catalytic catalytic JJ 1357 1364 subunit subunit NN 1365 1367 of of IN 1368 1371 PKA PKA NNP 1371 1372 . . . 1373 1377 This this DT 1378 1383 study study NN 1384 1393 indicates indicate VBZ 1394 1398 that that IN 1399 1409 activation activation NN 1410 1412 of of IN 1413 1416 PKA PKA NNP 1417 1424 reduces reduce VBZ 1425 1428 the the DT 1429 1438 induction induction NN 1439 1441 of of IN 1442 1443 a a DT 1444 1452 distinct distinct JJ 1453 1456 set set NN 1457 1459 of of IN 1460 1465 genes gene NNS 1466 1468 in in IN 1469 1478 monocytes monocyte NNS 1479 1482 and and CC 1483 1494 endothelial endothelial JJ 1495 1500 cells cell NNS 1501 1503 by by IN 1504 1514 inhibiting inhibit VBG 1515 1533 NF-kappaB-mediated nf-kappab-mediated JJ 1534 1547 transcription transcription NN 1547 1548 . . .