0 9 Selective selective JJ 10 20 activation activation NN 21 24 and and CC 25 35 functional functional JJ 36 48 significance significance NN 49 51 of of IN 52 60 p38alpha p38alpha NN 61 78 mitogen-activated mitogen-activated JJ 79 86 protein protein NN 87 93 kinase kinase NNP 94 96 in in IN 97 126 lipopolysaccharide-stimulated lipopolysaccharide-stimulated JJ 127 138 neutrophils neutrophil NNS 138 139 . . . 141 151 Activation Activation NNP 152 154 of of IN 155 165 leukocytes leukocyte NNS 166 168 by by IN 169 184 proinflammatory proinflammatory JJ 185 192 stimuli stimulus NNS 193 204 selectively selectively RB 205 214 initiates initiate VBZ 215 228 intracellular intracellular JJ 229 235 signal signal NN 236 248 transduction transduction NN 249 252 via via IN 253 263 sequential sequential JJ 264 279 phosphorylation phosphorylation NN 280 282 of of IN 283 290 kinases kinase NNS 290 291 . . . 292 310 Lipopolysaccharide Lipopolysaccharide NNP 311 312 ( ( ( 312 315 LPS LPS NNP 315 316 ) ) ) 317 328 stimulation stimulation NN 329 331 of of IN 332 337 human human JJ 338 349 neutrophils neutrophil NNS 350 352 is be VBZ 353 358 known know VBN 359 361 to to TO 362 368 result result VB 369 371 in in IN 372 382 activation activation NN 383 385 of of IN 386 389 p38 p38 NN 390 407 mitogen-activated mitogen-activated JJ 408 415 protein protein NN 416 422 kinase kinase NNP 423 424 ( ( ( 424 428 MAPk MAPk NNP 428 429 ) ) ) 429 430 ; ; : 431 438 however however RB 438 439 , , , 440 443 the the DT 444 452 upstream upstream JJ 453 465 activator(s) activator(s) NN 466 468 of of IN 469 472 p38 p38 NN 473 477 MAPk MAPk NNP 478 480 is be VBZ 481 488 unknown unknown JJ 488 489 , , , 490 493 and and CC 494 506 consequences consequence NNS 507 509 of of IN 510 513 p38 p38 NN 514 518 MAPk MAPk NNP 519 529 activation activation NN 530 536 remain remain VBP 537 544 largely largely RB 545 554 undefined undefined JJ 554 555 . . . 556 558 We we PRP 559 571 investigated investigate VBD 572 575 the the DT 576 580 MAPk MAPk NNP 581 587 kinase kinase NNP 588 589 ( ( ( 589 592 MKK MKK NNP 592 593 ) ) ) 594 598 that that WDT 599 608 activates activate VBZ 609 612 p38 p38 NN 613 617 MAPk mapk NN 618 620 in in IN 621 629 response response NN 630 632 to to TO 633 636 LPS LPS NNP 636 637 , , , 638 641 the the DT 642 645 p38 p38 NN 646 650 MAPk MAPk NNP 651 659 isoforms isoform NNS 660 664 that that WDT 665 668 are be VBP 669 678 activated activate VBN 679 681 as as IN 682 686 part part NN 687 689 of of IN 690 694 this this DT 695 702 pathway pathway NN 702 703 , , , 704 707 and and CC 708 711 the the DT 712 722 functional functional JJ 723 732 responses response NNS 733 741 affected affect VBN 742 744 by by IN 745 748 p38 p38 NN 749 753 MAPk MAPk NNP 754 764 activation activation NN 764 765 . . . 766 774 Although although IN 775 779 MKK3 MKK3 NNP 779 780 , , , 781 785 MKK4 MKK4 NNP 785 786 , , , 787 790 and and CC 791 795 MKK6 MKK6 NNP 796 799 all all DT 800 809 activated activate VBN 810 813 p38 p38 NN 814 818 MAPk mapk NN 819 821 in in IN 822 834 experimental experimental JJ 835 841 models model NNS 841 842 , , , 843 847 only only RB 848 852 MKK3 mkk3 NN 853 856 was be VBD 857 862 found find VBN 863 865 to to TO 866 874 activate activate VB 875 886 recombinant recombinant JJ 887 890 p38 p38 NN 891 895 MAPk mapk NN 896 898 in in IN 899 910 LPS-treated lps-treated JJ 911 922 neutrophils neutrophil NNS 922 923 . . . 924 926 Of of IN 927 930 p38 p38 NN 931 935 MAPk MAPk NNP 936 944 isoforms isoform NNS 945 952 studied study VBN 952 953 , , , 954 958 only only RB 959 967 p38alpha p38alpha NN 968 971 and and CC 972 980 p38delta p38delta NN 981 985 were be VBD 986 994 detected detect VBN 995 997 in in IN 998 1009 neutrophils neutrophil NNS 1009 1010 . . . 1011 1014 LPS LPS NNP 1015 1026 stimulation stimulation NN 1027 1038 selectively selectively RB 1039 1048 activated activate VBD 1049 1057 p38alpha p38alpha NN 1057 1058 . . . 1059 1067 Specific specific JJ 1068 1078 inhibitors inhibitor NNS 1079 1081 of of IN 1082 1090 p38alpha p38alpha NN 1091 1095 MAPk MAPk NNP 1096 1103 blocked block VBD 1104 1115 LPS-induced lps-induced JJ 1116 1124 adhesion adhesion NN 1124 1125 , , , 1126 1133 nuclear nuclear JJ 1134 1146 factor-kappa factor-kappa NN 1147 1148 B B NNP 1149 1150 ( ( ( 1150 1159 NF-kappaB NF-kappaB NNP 1159 1160 ) ) ) 1161 1171 activation activation NN 1171 1172 , , , 1173 1176 and and CC 1177 1186 synthesis synthesis NN 1187 1189 of of IN 1190 1195 tumor tumor NN 1196 1204 necrosis necrosis NN 1205 1217 factor-alpha factor-alpha NN 1218 1219 ( ( ( 1219 1228 TNF-alpha TNF-alpha NNP 1228 1229 ) ) ) 1229 1230 . . . 1231 1241 Inhibition Inhibition NNP 1242 1244 of of IN 1245 1253 p38alpha p38alpha NN 1254 1258 MAPk MAPk NNP 1259 1267 resulted result VBD 1268 1270 in in IN 1271 1272 a a DT 1273 1282 transient transient JJ 1283 1291 decrease decrease NN 1292 1294 in in IN 1295 1304 TNF-alpha TNF-alpha NNP 1305 1309 mRNA mRNA NNP 1310 1322 accumulation accumulation NN 1323 1326 but but CC 1327 1337 persistent persistent JJ 1338 1342 loss loss NN 1343 1345 of of IN 1346 1355 TNF-alpha TNF-alpha NNP 1356 1365 synthesis synthesis NN 1365 1366 . . . 1367 1372 These these DT 1373 1381 findings finding NNS 1382 1389 support support VBP 1390 1391 a a DT 1392 1399 pathway pathway NN 1400 1402 by by IN 1403 1408 which which WDT 1409 1412 LPS lps NN 1413 1424 stimulation stimulation NN 1425 1427 of of IN 1428 1439 neutrophils neutrophil NNS 1440 1447 results result VBZ 1448 1450 in in IN 1451 1461 activation activation NN 1462 1464 of of IN 1465 1469 MKK3 MKK3 NNP 1469 1470 , , , 1471 1476 which which WDT 1477 1479 in in IN 1480 1484 turn turn NN 1485 1494 activates activate VBZ 1495 1503 p38alpha p38alpha NN 1504 1508 MAPk MAPk NNP 1508 1509 , , , 1510 1520 ultimately ultimately RB 1521 1531 regulating regulate VBG 1532 1540 adhesion adhesion NN 1540 1541 , , , 1542 1551 NF-kappaB NF-kappaB NNP 1552 1562 activation activation NN 1562 1563 , , , 1564 1572 enhanced enhance VBD 1573 1577 gene gene NN 1578 1588 expression expression NN 1589 1591 of of IN 1592 1601 TNF-alpha TNF-alpha NNP 1601 1602 , , , 1603 1606 and and CC 1607 1617 regulation regulation NN 1618 1620 of of IN 1621 1630 TNF-alpha TNF-alpha NNP 1631 1640 synthesis synthesis NN 1640 1641 . . .