0 9 NF-kappaB NF-kappaB NNP 10 20 activation activation NN 21 23 is be VBZ 24 32 required require VBN 33 36 for for IN 37 48 C5a-induced c5a-induced JJ 49 62 interleukin-8 interleukin-8 NN 63 67 gene gene NN 68 78 expression expression NN 79 81 in in IN 82 93 mononuclear mononuclear JJ 94 99 cells cell NNS 99 100 . . . 102 105 C5a C5a NNP 105 106 , , , 107 108 a a DT 109 115 potent potent JJ 116 123 peptide peptide NN 124 139 chemoattractant chemoattractant NN 139 140 , , , 141 151 stimulates stimulate VBZ 152 165 interleukin-8 interleukin-8 NN 166 167 ( ( ( 167 171 IL-8 il-8 NN 171 172 ) ) ) 173 182 secretion secretion NN 183 187 from from IN 188 198 peripheral peripheral JJ 199 204 blood blood NN 205 216 mononuclear mononuclear JJ 217 222 cells cell NNS 223 224 ( ( ( 224 228 PBMC PBMC NNP 228 229 ) ) ) 229 230 . . . 231 242 Experiments experiment NNS 243 247 were be VBD 248 257 conducted conduct VBN 258 260 to to TO 261 271 understand understand VB 272 275 the the DT 276 286 mechanisms mechanism NNS 287 290 for for IN 291 302 C5a-induced c5a-induced JJ 303 307 IL-8 il-8 NN 308 318 production production NN 318 319 , , , 320 325 which which WDT 326 329 was be VBD 330 337 14-fold 14-fold RB 338 345 greater great JJR 346 350 than than IN 351 355 that that DT 356 358 in in IN 359 371 unstimulated unstimulated JJ 372 377 cells cell NNS 378 380 by by IN 381 382 2 2 CD 383 388 hours hour NNS 388 389 . . . 390 394 IL-8 il-8 NN 395 404 secretion secretion NN 405 408 was be VBD 409 420 accompanied accompany VBN 421 423 by by IN 424 436 accumulation accumulation NN 437 439 of of IN 440 444 IL-8 IL-8 NNP 445 449 mRNA mRNA NNP 450 452 in in IN 453 456 the the DT 457 464 cytosol cytosol NN 465 468 and and CC 469 471 by by IN 472 479 nuclear nuclear JJ 480 490 expression expression NN 491 493 of of IN 494 495 a a DT 496 502 kappaB kappab NN 503 506 DNA dna NN 507 514 binding binding NN 515 523 activity activity NN 524 530 within within IN 531 533 30 30 CD 534 541 minutes minute NNS 541 542 . . . 543 547 AP-1 ap-1 NN 548 551 but but CC 552 555 not not RB 556 563 NF-IL-6 NF-IL-6 NNP 564 567 DNA DNA NNP 568 575 binding binding NN 576 584 activity activity NN 585 588 was be VBD 589 593 also also RB 594 602 detected detect VBN 603 605 in in IN 606 620 C5a-stimulated c5a-stimulated JJ 621 625 PBMC PBMC NNP 625 626 ; ; : 627 634 however however RB 634 635 , , , 636 639 its its PRP$ 640 647 delayed delay VBN 648 658 expression expression NN 659 660 ( ( ( 660 667 maximal maximal JJ 668 670 at at IN 671 672 4 4 CD 673 678 hours hour NNS 678 679 ) ) ) 680 689 suggested suggest VBD 690 691 a a DT 692 696 less less RBR 697 706 important important JJ 707 711 role role NN 712 714 in in IN 715 718 the the DT 719 724 rapid rapid JJ 725 735 production production NN 736 738 of of IN 739 743 IL-8 il-8 NN 743 744 . . . 745 748 The the DT 749 760 correlation correlation NN 761 768 between between IN 769 780 C5a-induced c5a-induced JJ 781 787 kappaB kappaB NNP 788 795 binding binding NN 796 804 activity activity NN 805 808 and and CC 809 813 IL-8 il-8 NN 814 818 gene gene NN 819 829 expression expression NN 830 833 was be VBD 834 842 examined examine VBN 843 845 in in IN 846 849 the the DT 850 858 RAW264.7 raw264.7 NN 859 869 macrophage macrophage NN 870 875 cells cell NNS 876 881 using use VBG 882 890 reporter reporter NN 891 896 genes gene NNS 897 905 directed direct VBN 906 908 by by IN 909 912 the the DT 913 919 kappaB kappab NN 920 928 sequence sequence NN 929 933 from from IN 934 946 IkappaBalpha IkappaBalpha NNP 947 950 and and CC 951 955 IL-8 IL-8 NNP 956 964 promoter promoter NN 965 972 regions region NNS 972 973 . . . 974 985 C5a-induced c5a-induced JJ 986 994 reporter reporter NN 995 999 gene gene NN 1000 1010 expression expression NN 1011 1014 was be VBD 1015 1024 abolished abolish VBN 1025 1027 by by IN 1028 1039 introducing introduce VBG 1040 1049 mutations mutation NNS 1050 1054 into into IN 1055 1058 the the DT 1059 1065 kappaB kappab NN 1066 1071 sites site NNS 1072 1075 and and CC 1076 1078 by by IN 1079 1091 coexpression coexpression NN 1092 1094 of of IN 1095 1096 a a DT 1097 1105 dominant dominant JJ 1106 1114 negative negative JJ 1115 1127 IkappaBalpha IkappaBalpha NNP 1128 1137 construct construct NN 1138 1147 resistant resistant JJ 1148 1150 to to TO 1151 1166 agonist-induced agonist-induced JJ 1167 1182 phosphorylation phosphorylation NN 1182 1183 . . . 1184 1193 Pertussis pertussis NN 1194 1199 toxin toxin NN 1199 1200 , , , 1201 1206 which which WDT 1207 1222 ADP-ribosylates adp-ribosylate VBZ 1223 1226 the the DT 1227 1229 Gi Gi NNP 1230 1238 proteins protein NNS 1239 1244 known know VBN 1245 1247 to to TO 1248 1254 couple couple VB 1255 1257 to to TO 1258 1261 the the DT 1262 1265 C5a C5a NNP 1266 1274 receptor receptor NN 1274 1275 , , , 1276 1284 produced produce VBD 1285 1292 minimal minimal JJ 1293 1303 inhibition inhibition NN 1304 1306 of of IN 1307 1318 C5a-induced c5a-induced JJ 1319 1323 IL-8 il-8 NN 1324 1334 expression expression NN 1335 1338 and and CC 1339 1342 had have VBD 1343 1349 little little JJ 1350 1356 effect effect NN 1357 1359 on on IN 1360 1371 C5a-induced c5a-induced JJ 1372 1379 calcium calcium NN 1380 1392 mobilization mobilization NN 1393 1395 in in IN 1396 1404 RAW264.7 raw264.7 NN 1405 1410 cells cell NNS 1410 1411 . . . 1412 1417 These these DT 1418 1425 results result NNS 1426 1433 suggest suggest VBP 1434 1438 that that IN 1439 1448 NF-kappaB NF-kappaB NNP 1449 1459 activation activation NN 1460 1462 is be VBZ 1463 1471 required require VBN 1472 1475 for for IN 1476 1487 C5a-induced c5a-induced JJ 1488 1492 IL-8 il-8 NN 1493 1497 gene gene NN 1498 1508 expression expression NN 1509 1512 and and CC 1513 1517 that that IN 1518 1522 this this DT 1523 1531 response response NN 1532 1534 is be VBZ 1535 1543 mediated mediate VBN 1544 1553 primarily primarily RB 1554 1561 through through IN 1562 1563 a a DT 1564 1573 pertussis pertussis NN 1574 1591 toxin-insensitive toxin-insensitive JJ 1592 1599 pathway pathway NN 1599 1600 . . .