0 7 Aspirin aspirin NN 8 16 inhibits inhibit VBZ 17 24 nuclear nuclear JJ 25 37 factor-kappa factor-kappa NN 38 39 B B NNP 40 52 mobilization mobilization NN 53 56 and and CC 57 65 monocyte monocyte NN 66 74 adhesion adhesion NN 75 77 in in IN 78 88 stimulated stimulate VBN 89 94 human human JJ 95 106 endothelial endothelial JJ 107 112 cells cell NNS 112 113 . . . 115 125 BACKGROUND background NN 125 126 : : : 127 130 The the DT 131 140 induction induction NN 141 143 of of IN 144 152 vascular vascular JJ 153 157 cell cell NN 158 166 adhesion adhesion NN 167 177 molecule-1 molecule-1 NN 178 179 ( ( ( 179 185 VCAM-1 vcam-1 NN 185 186 ) ) ) 187 190 and and CC 191 201 E-selectin E-selectin NNP 202 204 by by IN 205 210 tumor tumor NN 211 219 necrosis necrosis NN 220 232 factor-alpha factor-alpha NN 233 234 ( ( ( 234 237 TNF TNF NNP 237 238 ) ) ) 239 241 is be VBZ 242 250 mediated mediate VBN 251 253 by by IN 254 266 mobilization mobilization NN 267 269 of of IN 270 273 the the DT 274 287 transcription transcription NN 288 294 factor factor NN 295 302 nuclear nuclear JJ 303 315 factor-kappa factor-kappa NN 316 317 B B NNP 318 319 ( ( ( 319 327 NF-kappa NF-kappa NNP 328 329 B B NNP 329 330 ) ) ) 330 331 . . . 332 337 Since since IN 338 349 salicylates salicylate NNS 350 354 have have VBP 355 359 been be VBN 360 368 reported report VBN 369 371 to to TO 372 379 inhibit inhibit VB 380 388 NF-kappa NF-kappa NNP 389 390 B B NNP 391 401 activation activation NN 402 404 by by IN 405 415 preventing prevent VBG 416 419 the the DT 420 431 degradation degradation NN 432 434 of of IN 435 438 its its PRP$ 439 448 inhibitor inhibitor NN 449 450 I i NN 451 456 kappa kappa NN 457 458 B B NNP 458 459 , , , 460 462 we we PRP 463 470 studied study VBD 471 472 a a DT 473 482 potential potential JJ 483 493 inhibition inhibition NN 494 496 of of IN 497 501 this this DT 502 509 pathway pathway NN 510 512 by by IN 513 529 acetylsalicylate acetylsalicylate NN 530 531 ( ( ( 531 538 aspirin aspirin NN 538 539 ) ) ) 540 542 in in IN 543 548 human human JJ 549 558 umbilical umbilical JJ 559 563 vein vein NN 564 575 endothelial endothelial JJ 576 581 cells cell NNS 582 583 ( ( ( 583 589 HUVECs HUVEC NNP 589 590 ) ) ) 590 591 . . . 592 599 METHODS methods NNS 600 603 AND and CC 604 611 RESULTS results NNS 611 612 : : : 613 622 Gel-shift gel-shift JJ 623 631 analyses analysis NNS 632 644 demonstrated demonstrate VBD 645 659 dose-dependent dose-dependent JJ 660 670 inhibition inhibition NN 671 673 of of IN 674 685 TNF-induced tnf-induced JJ 686 694 NF-kappa NF-kappa NNP 695 696 B B NNP 697 709 mobilization mobilization NN 710 712 by by IN 713 720 aspirin aspirin NN 721 723 at at IN 724 738 concentrations concentration NNS 739 746 ranging range VBG 747 751 from from IN 752 753 1 1 CD 754 756 to to TO 757 759 10 10 CD 760 767 mmol/L. mmol/l. NN 768 777 Induction induction NN 778 780 of of IN 781 787 VCAM-1 VCAM-1 NNP 788 791 and and CC 792 802 E-selectin E-selectin NNP 803 810 surface surface NN 811 821 expression expression NN 822 824 by by IN 825 828 TNF TNF NNP 829 832 was be VBD 833 849 dose-dependently dose-dependently RB 850 857 reduced reduce VBN 858 860 by by IN 861 868 aspirin aspirin NN 869 873 over over IN 874 877 the the DT 878 882 same same JJ 883 888 range range NN 888 889 , , , 890 895 while while IN 896 905 induction induction NN 906 908 of of IN 909 922 intercellular intercellular JJ 923 931 adhesion adhesion NN 932 942 molecule-1 molecule-1 NN 943 944 ( ( ( 944 950 ICAM-1 icam-1 NN 950 951 ) ) ) 952 955 was be VBD 956 962 hardly hardly RB 963 971 affected affect VBN 971 972 . . . 973 980 Aspirin aspirin NN 981 989 appeared appear VBD 990 992 to to TO 993 1000 prevent prevent VB 1001 1007 VCAM-1 vcam-1 NN 1008 1021 transcription transcription NN 1021 1022 , , , 1023 1028 since since IN 1029 1031 it it PRP 1032 1048 dose-dependently dose-dependently RB 1049 1058 inhibited inhibit VBD 1059 1068 induction induction NN 1069 1071 of of IN 1072 1078 VCAM-1 VCAM-1 NNP 1079 1083 mRNA mRNA NNP 1084 1086 by by IN 1087 1090 TNF TNF NNP 1090 1091 . . . 1092 1094 As as IN 1095 1096 a a DT 1097 1107 functional functional JJ 1108 1119 consequence consequence NN 1119 1120 , , , 1121 1129 adhesion adhesion NN 1130 1132 of of IN 1133 1137 U937 u937 NN 1138 1147 monocytes monocyte NNS 1148 1150 to to TO 1151 1165 TNF-stimulated tnf-stimulated JJ 1166 1172 HUVECs huvec NNS 1173 1176 was be VBD 1177 1185 markedly markedly RB 1186 1193 reduced reduce VBN 1194 1196 by by IN 1197 1204 aspirin aspirin NN 1205 1208 due due JJ 1209 1211 to to TO 1212 1223 suppression suppression NN 1224 1226 of of IN 1227 1233 VCAM-1 VCAM-1 NNP 1234 1237 and and CC 1238 1248 E-selectin E-selectin NNP 1249 1261 upregulation upregulation NN 1261 1262 . . . 1263 1268 These these DT 1269 1276 effects effect NNS 1277 1279 of of IN 1280 1287 aspirin aspirin NN 1288 1292 were be VBD 1293 1296 not not RB 1297 1304 related related JJ 1305 1307 to to TO 1308 1311 the the DT 1312 1322 inhibition inhibition NN 1323 1325 of of IN 1326 1340 cyclooxygenase cyclooxygenase NN 1341 1349 activity activity NN 1349 1350 , , , 1351 1356 since since IN 1357 1369 indomethacin indomethacin NN 1370 1373 was be VBD 1374 1385 ineffective ineffective JJ 1385 1386 . . . 1387 1398 CONCLUSIONS conclusions NNS 1398 1399 : : : 1400 1403 Our our PRP$ 1404 1408 data datum NNS 1409 1416 suggest suggest VBP 1417 1421 that that IN 1422 1429 aspirin aspirin NN 1430 1438 inhibits inhibit VBZ 1439 1447 NF-kappa NF-kappa NNP 1448 1449 B B NNP 1450 1462 mobilization mobilization NN 1462 1463 , , , 1464 1473 induction induction NN 1474 1476 of of IN 1477 1483 VCAM-1 VCAM-1 NNP 1484 1487 and and CC 1488 1498 E-selectin E-selectin NNP 1498 1499 , , , 1500 1503 and and CC 1504 1514 subsequent subsequent JJ 1515 1523 monocyte monocyte NN 1524 1532 adhesion adhesion NN 1533 1535 in in IN 1536 1547 endothelial endothelial JJ 1548 1553 cells cell NNS 1554 1564 stimulated stimulate VBN 1565 1567 by by IN 1568 1571 TNF TNF NNP 1571 1572 , , , 1573 1580 thereby thereby RB 1581 1590 providing provide VBG 1591 1593 an an DT 1594 1604 additional additional JJ 1605 1614 mechanism mechanism NN 1615 1618 for for IN 1619 1630 therapeutic therapeutic JJ 1631 1638 effects effect NNS 1639 1641 of of IN 1642 1649 aspirin aspirin NN 1649 1650 . . .