0 13 CD14-mediated cd14-mediated JJ 14 27 translocation translocation NN 28 30 of of IN 31 38 nuclear nuclear JJ 39 51 factor-kappa factor-kappa NN 52 53 B b NN 54 61 induced induce VBN 62 64 by by IN 65 83 lipopolysaccharide lipopolysaccharide NN 84 88 does do VBZ 89 92 not not RB 93 100 require require VB 101 109 tyrosine tyrosine NN 110 116 kinase kinase NNP 117 125 activity activity NN 125 126 . . . 128 134 During during IN 135 138 the the DT 139 145 course course NN 146 148 of of IN 149 156 serious serious JJ 157 166 bacterial bacterial JJ 167 177 infections infection NNS 177 178 , , , 179 197 lipopolysaccharide lipopolysaccharide NN 198 199 ( ( ( 199 202 LPS LPS NNP 202 203 ) ) ) 204 206 is be VBZ 207 215 believed believe VBN 216 218 to to TO 219 227 interact interact VB 228 232 with with IN 233 243 macrophage macrophage NN 244 253 receptors receptor NNS 253 254 , , , 255 264 resulting result VBG 265 267 in in IN 268 271 the the DT 272 282 generation generation NN 283 285 of of IN 286 298 inflammatory inflammatory JJ 299 308 mediators mediator NNS 309 312 and and CC 313 321 systemic systemic JJ 322 330 symptoms symptom NNS 331 340 including include VBG 341 352 hemodynamic hemodynamic JJ 353 364 instability instability NN 365 368 and and CC 369 374 shock shock NN 374 375 . . . 376 380 CD14 cd14 NN 380 381 , , , 382 383 a a DT 384 419 glycosylphosphatidylinositol-linked glycosylphosphatidylinositol-linked JJ 420 427 antigen antigen NN 427 428 , , , 429 438 functions function VBZ 439 441 as as IN 442 444 an an DT 445 448 LPS lps NN 449 458 signaling signaling NN 459 467 receptor receptor NN 467 468 . . . 469 470 A a DT 471 479 critical critical JJ 480 485 issue issue NN 486 494 concerns concern VBZ 495 498 the the DT 499 508 mechanism mechanism NN 509 511 by by IN 512 517 which which WDT 518 522 CD14 cd14 NN 522 523 , , , 524 529 which which WDT 530 533 has have VBZ 534 536 no no DT 537 550 transmembrane transmembrane JJ 551 557 domain domain NN 557 558 , , , 559 569 transduces transduce VBZ 570 573 its its PRP$ 574 580 signal signal NN 581 590 following follow VBG 591 594 LPS lps NN 595 602 binding binding NN 602 603 . . . 604 612 Recently recently RB 612 613 , , , 614 627 investigators investigator NNS 628 632 have have VBP 633 645 hypothesized hypothesize VBN 646 650 that that IN 651 664 CD14-mediated cd14-mediated JJ 665 674 signaling signaling NN 675 677 is be VBZ 678 686 effected effect VBN 687 694 through through IN 695 696 a a DT 697 716 receptor-associated receptor-associated JJ 717 725 tyrosine tyrosine NN 726 732 kinase kinase NNP 733 734 ( ( ( 734 736 TK TK NNP 736 737 ) ) ) 737 738 , , , 739 749 suggesting suggest VBG 750 751 a a DT 752 766 multicomponent multicomponent JJ 767 775 receptor receptor NN 776 781 model model NN 782 784 of of IN 785 788 LPS lps NN 789 798 signaling signaling NN 798 799 . . . 800 809 Wild-type wild-type JJ 810 817 Chinese chinese JJ 818 825 hamster hamster NN 826 831 ovary ovary NN 832 833 ( ( ( 833 840 CHO)-K1 cho)-k1 NN 841 846 cells cell NNS 847 850 can can MD 851 853 be be VB 854 863 activated activate VBN 864 866 by by IN 867 876 endotoxin endotoxin NN 877 879 to to TO 880 887 release release VB 888 900 arachidonate arachidonate NN 901 910 following follow VBG 911 923 transfection transfection NN 924 928 with with IN 929 934 human human JJ 935 939 CD14 cd14 NN 940 941 ( ( ( 941 949 CHO/CD14 cho/cd14 NN 949 950 ) ) ) 950 951 . . . 952 959 Nuclear nuclear JJ 960 973 translocation translocation NN 974 976 of of IN 977 986 cytosolic cytosolic JJ 987 995 NF-kappa NF-kappa NNP 996 997 B B NNP 998 1000 is be VBZ 1001 1011 correlated correlate VBN 1012 1016 with with IN 1017 1018 a a DT 1019 1025 number number NN 1026 1028 of of IN 1029 1042 LPS-inducible lps-inducible JJ 1043 1052 responses response NNS 1052 1053 . . . 1054 1056 We we PRP 1057 1063 sought seek VBD 1064 1066 to to TO 1067 1076 determine determine VB 1077 1079 if if IN 1080 1084 this this DT 1085 1092 pathway pathway NN 1093 1097 were be VBD 1098 1105 present present JJ 1106 1108 in in IN 1109 1117 CHO/CD14 cho/cd14 NN 1118 1123 cells cell NNS 1124 1127 and and CC 1128 1130 to to TO 1131 1140 elucidate elucidate VB 1141 1144 the the DT 1145 1157 relationship relationship NN 1158 1160 of of IN 1161 1169 NF-kappa NF-kappa NNP 1170 1171 B B NNP 1172 1182 activation activation NN 1183 1185 to to TO 1186 1189 the the DT 1190 1194 CD14 cd14 NN 1195 1203 receptor receptor NN 1204 1210 system system NN 1210 1211 . . . 1212 1226 LPS-stimulated lps-stimulated JJ 1227 1240 translocation translocation NN 1241 1243 of of IN 1244 1252 NF-kappa NF-kappa NNP 1253 1254 B B NNP 1255 1257 in in IN 1258 1266 CHO/CD14 cho/cd14 NN 1267 1272 cells cell NNS 1273 1282 resembled resemble VBD 1283 1286 the the DT 1287 1291 same same JJ 1292 1300 response response NN 1301 1303 in in IN 1304 1307 the the DT 1308 1314 murine murine JJ 1315 1330 macrophage-like macrophage-like JJ 1331 1335 cell cell NN 1336 1340 line line NN 1341 1344 RAW RAW NNP 1345 1350 264.7 264.7 CD 1350 1351 . . . 1352 1359 Protein protein NN 1360 1369 synthesis synthesis NN 1370 1380 inhibitors inhibitor NNS 1381 1384 and and CC 1385 1400 corticosteroids corticosteroid NNS 1400 1401 , , , 1402 1407 which which WDT 1408 1416 suppress suppress VBP 1417 1429 arachidonate arachidonate NN 1430 1437 release release NN 1438 1441 and and CC 1442 1445 the the DT 1446 1455 synthesis synthesis NN 1456 1458 of of IN 1459 1474 proinflammatory proinflammatory JJ 1475 1484 cytokines cytokine NNS 1484 1485 , , , 1486 1489 had have VBD 1490 1492 no no DT 1493 1499 effect effect NN 1500 1502 on on IN 1503 1516 translocation translocation NN 1517 1519 of of IN 1520 1528 NF-kappa NF-kappa NNP 1529 1530 B B NNP 1531 1533 in in IN 1534 1542 CHO/CD14 cho/cd14 NN 1543 1545 or or CC 1546 1549 RAW RAW NNP 1550 1555 264.7 264.7 CD 1556 1561 cells cell NNS 1561 1562 , , , 1563 1576 demonstrating demonstrate VBG 1577 1581 that that IN 1582 1590 NF-kappa NF-kappa NNP 1591 1592 B B NNP 1593 1606 translocation translocation NN 1607 1609 is be VBZ 1610 1612 an an DT 1613 1618 early early JJ 1619 1624 event event NN 1624 1625 . . . 1626 1634 Although although IN 1635 1637 TK TK NNP 1638 1646 activity activity NN 1647 1650 was be VBD 1651 1663 consistently consistently RB 1664 1672 observed observe VBN 1673 1675 by by IN 1676 1690 immunoblotting immunoblotte VBG 1691 1699 extracts extract NNS 1700 1704 from from IN 1705 1714 activated activate VBN 1715 1718 RAW RAW NNP 1719 1724 264.7 264.7 CD 1725 1730 cells cell NNS 1730 1731 , , , 1732 1743 LPS-induced lps-induced JJ 1744 1759 phosphotyrosine phosphotyrosine NN 1760 1768 residues residue NNS 1769 1773 were be VBD 1774 1777 not not RB 1778 1786 observed observe VBN 1787 1791 from from IN 1792 1801 similarly similarly RB 1802 1809 treated treat VBN 1810 1818 CHO/CD14 cho/cd14 NN 1819 1824 cells cell NNS 1824 1825 . . . 1826 1837 Furthermore furthermore RB 1837 1838 , , , 1839 1842 the the DT 1843 1845 TK TK NNP 1846 1856 inhibitors inhibitor NNS 1857 1867 herbimycin herbimycin NN 1868 1869 A a NN 1870 1873 and and CC 1874 1883 genistein genistein NN 1884 1890 failed fail VBD 1891 1893 to to TO 1894 1901 inhibit inhibit VB 1902 1915 translocation translocation NN 1916 1918 of of IN 1919 1927 NF-kappa NF-kappa NNP 1928 1929 B B NNP 1930 1932 in in IN 1933 1941 CHO/CD14 cho/cd14 NN 1942 1944 or or CC 1945 1948 RAW RAW NNP 1949 1954 264.7 264.7 CD 1955 1960 cells cell NNS 1960 1961 , , , 1962 1970 although although IN 1971 1975 both both DT 1976 1978 of of IN 1979 1984 these these DT 1985 1991 agents agent NNS 1992 2001 inhibited inhibit VBD 2002 2013 LPS-induced lps-induced JJ 2014 2016 TK TK NNP 2017 2025 activity activity NN 2026 2028 in in IN 2029 2032 RAW RAW NNP 2033 2038 264.7 264.7 CD 2039 2044 cells cell NNS 2044 2045 . . . 2046 2051 These these DT 2052 2059 results result NNS 2060 2065 imply imply VBP 2066 2070 that that IN 2071 2073 TK TK NNP 2074 2082 activity activity NN 2083 2085 is be VBZ 2086 2089 not not RB 2090 2100 obligatory obligatory JJ 2101 2104 for for IN 2105 2118 CD14-mediated cd14-mediated JJ 2119 2125 signal signal NN 2126 2138 transduction transduction NN 2139 2141 to to TO 2142 2147 occur occur VB 2148 2150 in in IN 2151 2159 response response NN 2160 2162 to to TO 2163 2166 LPS LPS NNP 2166 2167 . . .