0 23 Extracellular-regulated extracellular-regulated JJ 24 30 kinase kinase NNP 31 34 1/2 1/2 CD 34 35 , , , 36 39 Jun Jun NNP 40 50 N-terminal n-terminal JJ 51 57 kinase kinase NNP 57 58 , , , 59 62 and and CC 63 68 c-Jun c-jun NN 69 72 are be VBP 73 81 involved involve VBN 82 84 in in IN 85 93 NF-kappa NF-kappa NNP 94 105 B-dependent b-dependent JJ 106 110 IL-6 IL-6 NNP 111 121 expression expression NN 122 124 in in IN 125 130 human human JJ 131 140 monocytes monocyte NNS 140 141 . . . 143 145 In in IN 146 149 the the DT 150 157 present present JJ 158 163 study study NN 164 166 we we PRP 167 179 investigated investigate VBD 180 183 the the DT 184 192 possible possible JJ 193 204 involvement involvement NN 205 207 of of IN 208 211 the the DT 212 229 mitogen-activated mitogen-activated JJ 230 237 protein protein NN 238 244 kinase kinase NNP 245 251 family family NN 252 259 members member NNS 260 283 extracellular-regulated extracellular-regulated JJ 284 290 kinase kinase NNP 291 294 1/2 1/2 CD 295 296 ( ( ( 296 302 ERK1/2 ERK1/2 NNP 302 303 ) ) ) 304 307 and and CC 308 313 c-Jun c-jun NN 314 324 N-terminal n-terminal JJ 325 331 kinase kinase NNP 332 333 ( ( ( 333 336 JNK JNK NNP 336 337 ) ) ) 338 340 in in IN 341 350 mediating mediate VBG 351 355 IL-6 il-6 NN 356 360 gene gene NN 361 371 expression expression NN 372 374 in in IN 375 380 human human JJ 381 390 monocytes monocyte NNS 390 391 , , , 392 394 in in IN 395 405 particular particular JJ 406 411 their their PRP$ 412 416 role role NN 417 419 in in IN 420 429 enhancing enhance VBG 430 438 NF-kappa NF-kappa NNP 439 440 B B NNP 441 449 activity activity NN 449 450 . . . 451 458 Freshly freshly RB 459 467 isolated isolate VBN 468 477 monocytes monocyte NNS 478 485 treated treat VBN 486 490 with with IN 491 494 the the DT 495 502 protein protein NN 503 514 phosphatase phosphatase NN 515 524 inhibitor inhibitor NN 525 532 okadaic okadaic JJ 533 537 acid acid NN 538 546 secreted secrete VBD 547 551 high high JJ 552 558 levels level NNS 559 561 of of IN 562 566 IL-6 il-6 NN 567 574 protein protein NN 574 575 , , , 576 581 which which WDT 582 591 coincided coincide VBD 592 596 with with IN 597 605 enhanced enhance VBN 606 613 binding binding NN 614 622 activity activity NN 623 625 of of IN 626 634 NF-kappa NF-kappa NNP 635 636 B B NNP 637 639 as as RB 640 644 well well RB 645 647 as as IN 648 652 with with IN 653 668 phosphorylation phosphorylation NN 669 672 and and CC 673 683 activation activation NN 684 686 of of IN 687 690 the the DT 691 697 ERK1/2 ERK1/2 NNP 698 701 and and CC 702 705 JNK JNK NNP 706 714 proteins protein NNS 714 715 . . . 716 719 The the DT 720 723 ERK ERK NNP 724 740 pathway-specific pathway-specific JJ 741 750 inhibitor inhibitor NN 751 758 PD98059 pd98059 NN 759 768 inhibited inhibit VBD 769 773 IL-6 il-6 NN 774 783 secretion secretion NN 784 788 from from IN 789 798 monocytes monocyte NNS 798 799 . . . 800 809 Transient transient JJ 810 824 overexpression overexpression NN 825 827 of of IN 828 836 inactive inactive JJ 837 844 mutants mutant NNS 845 847 of of IN 848 854 either either CC 855 860 Raf-1 Raf-1 NNP 861 863 or or CC 864 868 JNK1 JNK1 NNP 869 875 showed show VBD 876 880 that that IN 881 885 both both DT 886 894 pathways pathway NNS 895 899 were be VBD 900 908 involved involve VBN 909 911 in in IN 912 917 kappa kappa NN 918 929 B-dependent b-dependent JJ 930 934 IL-6 IL-6 NNP 935 943 promoter promoter NN 944 952 activity activity NN 952 953 . . . 954 956 By by IN 957 962 using use VBG 963 970 PD98059 pd98059 NN 970 971 , , , 972 974 we we PRP 975 987 demonstrated demonstrate VBD 988 992 that that IN 993 996 the the DT 997 1013 Raf1/MEK1/ERK1/2 Raf1/MEK1/ERK1/2 NNP 1014 1021 pathway pathway NN 1022 1025 did do VBD 1026 1029 not not RB 1030 1036 affect affect VB 1037 1040 the the DT 1041 1044 DNA dna NN 1045 1052 binding binding NN 1053 1055 of of IN 1056 1064 NF-kappa NF-kappa NNP 1065 1066 B B NNP 1067 1070 but but CC 1070 1071 , , , 1072 1078 rather rather RB 1078 1079 , , , 1080 1085 acted act VBD 1086 1088 at at IN 1089 1092 the the DT 1093 1098 level level NN 1099 1101 of of IN 1102 1117 transcriptional transcriptional JJ 1118 1126 activity activity NN 1127 1129 of of IN 1130 1138 NF-kappa NF-kappa NNP 1139 1141 B. B. NNP 1142 1155 Interestingly interestingly RB 1155 1156 , , , 1157 1159 it it PRP 1160 1163 was be VBD 1164 1169 shown show VBN 1170 1174 that that IN 1175 1183 NF-kappa NF-kappa NNP 1184 1194 B-mediated b-mediated JJ 1195 1199 gene gene NN 1200 1213 transcription transcription NN 1213 1214 , , , 1215 1219 both both CC 1220 1222 in in IN 1223 1226 the the DT 1227 1234 context context NN 1235 1237 of of IN 1238 1241 the the DT 1242 1246 IL-6 il-6 NN 1247 1255 promoter promoter NN 1256 1258 as as RB 1259 1263 well well RB 1264 1266 as as IN 1267 1269 on on IN 1270 1273 its its PRP$ 1274 1277 own own JJ 1277 1278 , , , 1279 1282 was be VBD 1283 1292 dependent dependent JJ 1293 1295 on on IN 1296 1300 both both CC 1301 1307 serine serine NN 1308 1314 kinase kinase NNP 1315 1323 activity activity NN 1324 1327 and and CC 1328 1339 interaction interaction NN 1340 1344 with with IN 1345 1350 c-Jun c-jun NN 1351 1358 protein protein NN 1358 1359 . . . 1360 1362 We we PRP 1363 1371 conclude conclude VBP 1372 1376 that that IN 1377 1384 okadaic okadaic JJ 1385 1397 acid-induced acid-induced JJ 1398 1402 IL-6 il-6 NN 1403 1407 gene gene NN 1408 1418 expression expression NN 1419 1421 is be VBZ 1422 1424 at at IN 1425 1430 least least JJS 1431 1437 partly partly RB 1438 1446 mediated mediate VBN 1447 1454 through through IN 1455 1458 the the DT 1459 1465 ERK1/2 ERK1/2 NNP 1466 1469 and and CC 1470 1473 JNK JNK NNP 1474 1491 pathway-dependent pathway-dependent JJ 1492 1502 activation activation NN 1503 1505 of of IN 1506 1514 NF-kappa NF-kappa NNP 1515 1516 B B NNP 1517 1532 transcriptional transcriptional JJ 1533 1541 capacity capacity NN 1541 1542 . . . 1543 1546 Our our PRP$ 1547 1554 results result NNS 1555 1562 suggest suggest VBP 1563 1567 that that IN 1568 1571 the the DT 1572 1575 JNK JNK NNP 1576 1583 pathway pathway NN 1584 1587 may may MD 1588 1596 regulate regulate VB 1597 1605 NF-kappa NF-kappa NNP 1606 1616 B-mediated b-mediated JJ 1617 1621 gene gene NN 1622 1635 transcription transcription NN 1636 1643 through through IN 1644 1647 its its PRP$ 1648 1663 phosphorylation phosphorylation NN 1664 1667 and and CC 1668 1678 activation activation NN 1679 1681 of of IN 1682 1687 c-Jun c-jun NN 1687 1688 . . .