0 7 Hypoxia Hypoxia NNP 8 16 enhances enhance VBZ 17 26 induction induction NN 27 29 of of IN 30 41 endothelial endothelial JJ 42 48 ICAM-1 icam-1 NN 48 49 : : : 50 54 role role NN 55 58 for for IN 59 68 metabolic metabolic JJ 69 77 acidosis acidosis NN 78 81 and and CC 82 93 proteasomes proteasome NNS 93 94 . . . 96 109 Intercellular intercellular JJ 110 118 adhesion adhesion NN 119 127 molecule molecule NN 128 129 1 1 CD 130 131 ( ( ( 131 137 ICAM-1 icam-1 NN 137 138 ) ) ) 139 141 is be VBZ 142 144 an an DT 145 154 important important JJ 155 163 molecule molecule NN 164 166 in in IN 167 176 promotion promotion NN 177 179 of of IN 180 197 polymorphonuclear polymorphonuclear JJ 198 208 neutrophil neutrophil NN 209 225 transendothelial transendothelial JJ 226 235 migration migration NN 236 242 during during IN 243 255 inflammation inflammation NN 255 256 . . . 257 267 Coincident coincident JJ 268 272 with with IN 273 277 many many JJ 278 290 inflammatory inflammatory JJ 291 299 diseases disease NNS 300 302 is be VBZ 303 309 tissue tissue NN 310 317 hypoxia hypoxia NN 317 318 . . . 319 323 Thus thus RB 324 326 we we PRP 327 339 hypothesized hypothesize VBD 340 344 that that IN 345 357 combinations combination NNS 358 360 of of IN 361 368 hypoxia hypoxia NN 369 372 and and CC 373 385 inflammatory inflammatory JJ 386 393 stimuli stimulus NNS 394 397 may may MD 398 412 differentially differentially RB 413 421 regulate regulate VB 422 432 expression expression NN 433 435 of of IN 436 447 endothelial endothelial JJ 448 454 ICAM-1 icam-1 NN 454 455 . . . 456 461 Human human JJ 462 473 endothelial endothelial JJ 474 479 cells cell NNS 480 484 were be VBD 485 492 exposed expose VBN 493 495 to to TO 496 503 hypoxia hypoxia NN 504 506 in in IN 507 510 the the DT 511 519 presence presence NN 520 522 or or CC 523 530 absence absence NN 531 533 of of IN 534 539 added add VBN 540 558 lipopolysaccharide lipopolysaccharide NN 559 560 ( ( ( 560 563 LPS LPS NNP 563 564 ) ) ) 565 568 and and CC 569 577 examined examine VBN 578 581 for for IN 582 592 expression expression NN 593 595 of of IN 596 606 functional functional JJ 607 613 ICAM-1 icam-1 NN 613 614 . . . 615 623 Although although IN 624 631 hypoxia hypoxia NN 632 637 alone alone RB 638 641 did do VBD 642 645 not not RB 646 652 induce induce VB 653 659 ICAM-1 icam-1 NN 659 660 , , , 661 664 the the DT 665 676 combination combination NN 677 679 of of IN 680 683 LPS lps NN 684 687 and and CC 688 695 hypoxia hypoxia NN 696 704 enhanced enhance VBD 705 706 ( ( ( 706 707 3 3 CD 708 711 +/- +/- SYM 712 720 0.4-fold 0.4-fold RB 721 725 over over IN 726 734 normoxia normoxia NN 734 735 ) ) ) 736 742 ICAM-1 icam-1 NN 743 753 expression expression NN 753 754 . . . 755 767 Combinations combination NNS 768 770 of of IN 771 778 hypoxia hypoxia NN 779 782 and and CC 783 786 LPS lps NN 787 800 significantly significantly RB 801 810 increased increase VBD 811 821 lymphocyte lymphocyte NN 822 829 binding binding NN 829 830 , , , 831 834 and and CC 835 839 such such JJ 840 849 increases increase NNS 850 854 were be VBD 855 864 inhibited inhibit VBN 865 867 by by IN 868 876 addition addition NN 877 879 of of IN 880 891 anti-ICAM-1 anti-icam-1 JJ 892 902 antibodies antibody NNS 903 905 or or CC 906 915 antisense antisense JJ 916 932 oligonucleotides oligonucleotide NNS 932 933 . . . 934 941 Hypoxic hypoxic JJ 942 952 endothelia endothelia NN 953 959 showed show VBD 960 961 a a DT 962 963 > > JJR 964 971 10-fold 10-fold JJ 972 980 increase increase NN 981 983 in in IN 984 995 sensitivity sensitivity NN 996 998 to to TO 999 1009 inhibitors inhibitor NNS 1010 1012 of of IN 1013 1023 proteasome proteasome NN 1024 1034 activation activation NN 1034 1035 , , , 1036 1039 and and CC 1040 1052 combinations combination NNS 1053 1055 of of IN 1056 1063 hypoxia hypoxia NN 1064 1067 and and CC 1068 1071 LPS lps NN 1072 1080 enhanced enhance VBD 1081 1101 proteasome-dependent proteasome-dependent JJ 1102 1124 cytoplasmic-to-nuclear cytoplasmic-to-nuclear JJ 1125 1137 localization localization NN 1138 1140 of of IN 1141 1144 the the DT 1145 1152 nuclear nuclear JJ 1153 1166 transcription transcription NN 1167 1179 factor-kappa factor-kappa NN 1180 1181 B B NNP 1182 1185 p65 p65 NN 1186 1187 ( ( ( 1187 1190 Rel Rel NNP 1191 1192 A A NNP 1192 1193 ) ) ) 1194 1201 subunit subunit NN 1201 1202 . . . 1203 1207 Such such JJ 1208 1218 proteasome proteasome NN 1219 1229 activation activation NN 1230 1240 correlated correlate VBD 1241 1245 with with IN 1246 1260 hypoxia-evoked hypoxia-evoked JJ 1261 1270 decreases decrease NNS 1271 1273 in in IN 1274 1278 both both CC 1279 1292 extracellular extracellular JJ 1293 1296 and and CC 1297 1310 intracellular intracellular JJ 1311 1313 pH ph NN 1313 1314 . . . 1315 1317 We we PRP 1318 1326 conclude conclude VBP 1327 1331 from from IN 1332 1337 these these DT 1338 1345 studies study NNS 1346 1350 that that IN 1351 1362 endothelial endothelial JJ 1363 1370 hypoxia hypoxia NN 1371 1379 provides provide VBZ 1380 1381 a a DT 1382 1387 novel novel JJ 1387 1388 , , , 1389 1409 proteasome-dependent proteasome-dependent JJ 1410 1418 stimulus stimulus NN 1419 1422 for for IN 1423 1429 ICAM-1 icam-1 NN 1430 1439 induction induction NN 1439 1440 . . .