0 9 Induction Induction NNP 10 12 of of IN 13 15 Mn Mn NNP 16 19 SOD SOD NNP 20 22 in in IN 23 28 human human JJ 29 38 monocytes monocyte NNS 39 46 without without IN 47 59 inflammatory inflammatory JJ 60 68 cytokine cytokine NN 69 79 production production NN 80 82 by by IN 83 84 a a DT 85 91 mutant mutant JJ 92 101 endotoxin endotoxin NN 101 102 . . . 104 113 Endotoxin Endotoxin NNP 114 125 selectively selectively RB 126 133 induces induce VBZ 134 142 monocyte monocyte NN 143 145 Mn Mn NNP 146 156 superoxide superoxide NN 157 166 dismutase dismutase NN 167 168 ( ( ( 168 171 SOD SOD NNP 171 172 ) ) ) 173 180 without without IN 181 190 affecting affect VBG 191 197 levels level NNS 198 200 of of IN 201 206 Cu,Zn Cu,Zn NNP 207 210 SOD SOD NNP 210 211 , , , 212 220 catalase catalase NN 220 221 , , , 222 224 or or CC 225 236 glutathione glutathione NN 237 247 peroxidase peroxidase NN 247 248 . . . 249 256 However however RB 256 257 , , , 258 264 little little JJ 265 267 is be VBZ 268 273 known know VBN 274 279 about about IN 280 283 the the DT 284 302 structure-activity structure-activity NN 303 315 relationship relationship NN 316 319 and and CC 320 323 the the DT 324 333 mechanism mechanism NN 334 336 by by IN 337 342 which which WDT 343 352 endotoxin endotoxin NN 353 360 induces induce VBZ 361 363 Mn Mn NNP 364 367 SOD SOD NNP 367 368 . . . 369 371 In in IN 372 376 this this DT 377 382 study study NN 383 385 we we PRP 386 398 demonstrated demonstrate VBD 399 403 that that IN 404 405 a a DT 406 412 mutant mutant JJ 413 424 Escherichia escherichia FW 425 429 coli coli FW 430 439 endotoxin endotoxin NN 440 447 lacking lack VBG 448 457 myristoyl myristoyl NN 458 463 fatty fatty JJ 464 468 acid acid NN 469 471 at at IN 472 475 the the DT 476 477 3 3 CD 477 478 ’ ' SYM 479 499 R-3-hydroxymyristate r-3-hydroxymyristate NN 500 508 position position NN 509 511 of of IN 512 515 the the DT 516 521 lipid lipid NN 522 523 A a NN 524 530 moiety moiety NN 531 539 retained retain VBD 540 543 its its PRP$ 544 548 full full JJ 549 557 capacity capacity NN 558 560 to to TO 561 570 coagulate coagulate VB 571 578 Limulus limulus NN 579 589 amoebocyte amoebocyte NN 590 596 lysate lysate NN 597 605 compared compare VBN 606 610 with with IN 611 614 the the DT 615 624 wild-type wild-type JJ 625 627 E. e. FW 628 632 coli coli FW 633 642 endotoxin endotoxin NN 643 646 and and CC 647 655 markedly markedly RB 656 666 stimulated stimulate VBD 667 670 the the DT 671 681 activation activation NN 682 684 of of IN 685 690 human human JJ 691 699 monocyte monocyte NN 700 707 nuclear nuclear JJ 708 721 factor-kappaB factor-kappab NN 722 725 and and CC 726 729 the the DT 730 739 induction induction NN 740 742 of of IN 743 745 Mn Mn NNP 746 749 SOD SOD NNP 750 754 mRNA mRNA NNP 755 758 and and CC 759 765 enzyme enzyme NN 766 774 activity activity NN 774 775 . . . 776 783 However however RB 783 784 , , , 785 787 in in IN 788 796 contrast contrast NN 797 799 to to TO 800 803 the the DT 804 813 wild-type wild-type JJ 814 823 endotoxin endotoxin NN 823 824 , , , 825 827 it it PRP 828 834 failed fail VBD 835 837 to to TO 838 844 induce induce VB 845 856 significant significant JJ 857 867 production production NN 868 870 of of IN 871 876 tumor tumor NN 877 885 necrosis necrosis NN 886 898 factor-alpha factor-alpha NN 899 902 and and CC 903 913 macrophage macrophage NN 914 926 inflammatory inflammatory JJ 927 941 protein-1alpha protein-1alpha NN 942 944 by by IN 945 954 monocytes monocyte NNS 955 958 and and CC 959 962 did do VBD 963 966 not not RB 967 973 induce induce VB 974 977 the the DT 978 993 phosphorylation phosphorylation NN 994 997 and and CC 998 1005 nuclear nuclear JJ 1006 1019 translocation translocation NN 1020 1022 of of IN 1023 1040 mitogen-activated mitogen-activated JJ 1041 1048 protein protein NN 1049 1055 kinase kinase NNP 1055 1056 . . . 1057 1062 These these DT 1063 1070 results result NNS 1071 1078 suggest suggest VBP 1079 1083 that that IN 1084 1085 1 1 LS 1085 1086 ) ) ) 1087 1092 lipid lipid NN 1093 1094 A a NN 1095 1104 myristoyl myristoyl NN 1105 1110 fatty fatty NN 1111 1115 acid acid NN 1115 1116 , , , 1117 1125 although although IN 1126 1128 it it PRP 1129 1131 is be VBZ 1132 1141 important important JJ 1142 1145 for for IN 1146 1149 the the DT 1150 1159 induction induction NN 1160 1162 of of IN 1163 1175 inflammatory inflammatory JJ 1176 1184 cytokine cytokine NN 1185 1195 production production NN 1196 1198 by by IN 1199 1204 human human JJ 1205 1214 monocytes monocyte NNS 1214 1215 , , , 1216 1218 is be VBZ 1219 1222 not not RB 1223 1232 necessary necessary JJ 1233 1236 for for IN 1237 1240 the the DT 1241 1250 induction induction NN 1251 1253 of of IN 1254 1256 Mn Mn NNP 1257 1260 SOD SOD NNP 1260 1261 , , , 1262 1263 2 2 LS 1263 1264 ) ) ) 1265 1283 endotoxin-mediated endotoxin-mediated JJ 1284 1293 induction induction NN 1294 1296 of of IN 1297 1299 Mn Mn NNP 1300 1303 SOD SOD NNP 1304 1307 and and CC 1308 1320 inflammatory inflammatory JJ 1321 1330 cytokines cytokine NNS 1331 1334 are be VBP 1335 1344 regulated regulate VBN 1344 1345 , , , 1346 1348 at at IN 1349 1354 least least JJS 1355 1357 in in IN 1358 1362 part part NN 1362 1363 , , , 1364 1371 through through IN 1372 1381 different different JJ 1382 1388 signal signal NN 1389 1401 transduction transduction NN 1402 1410 pathways pathway NNS 1410 1411 , , , 1412 1415 and and CC 1416 1417 3 3 LS 1417 1418 ) ) ) 1419 1426 failure failure NN 1427 1429 of of IN 1430 1433 the the DT 1434 1440 mutant mutant JJ 1441 1450 endotoxin endotoxin NN 1451 1453 to to TO 1454 1460 induce induce VB 1461 1466 tumor tumor NN 1467 1475 necrosis necrosis NN 1476 1488 factor-alpha factor-alpha NN 1489 1499 production production NN 1500 1502 is be VBZ 1502 1503 , , , 1504 1506 at at IN 1507 1512 least least JJS 1513 1515 in in IN 1516 1520 part part NN 1520 1521 , , , 1522 1525 due due IN 1526 1528 to to TO 1529 1532 its its PRP$ 1533 1542 inability inability NN 1543 1545 to to TO 1546 1554 activate activate VB 1555 1572 mitogen-activated mitogen-activated JJ 1573 1580 protein protein NN 1581 1587 kinase kinase NNP 1587 1588 . . .