0 14 Anti-Ehrlichia anti-ehrlichia FW 15 26 chaffeensis chaffeensis FW 27 35 antibody antibody NN 36 45 complexed complexe VBN 46 50 with with IN 51 53 E. e. FW 54 65 chaffeensis chaffeensis FW 66 73 induces induce VBZ 74 80 potent potent JJ 81 96 proinflammatory proinflammatory JJ 97 105 cytokine cytokine NN 106 110 mRNA mrna NN 111 121 expression expression NN 122 124 in in IN 125 130 human human JJ 131 140 monocytes monocyte NNS 141 148 through through IN 149 158 sustained sustained JJ 159 168 reduction reduction NN 169 171 of of IN 172 185 IkappaB-alpha IkappaB-alpha NNP 186 189 and and CC 190 200 activation activation NN 201 203 of of IN 204 213 NF-kappaB NF-kappaB NNP 213 214 . . . 216 225 Ehrlichia ehrlichia FW 226 237 chaffeensis chaffeensis FW 238 240 is be VBZ 241 243 an an DT 244 254 obligatory obligatory JJ 255 268 intracellular intracellular JJ 269 278 bacterium bacterium NN 279 283 that that WDT 284 291 infects infect VBZ 292 301 monocytes monocyte NNS 302 305 and and CC 306 317 macrophages macrophage NNS 318 321 and and CC 322 324 is be VBZ 325 328 the the DT 329 338 etiologic etiologic JJ 339 344 agent agent NN 345 347 of of IN 348 353 human human JJ 354 366 ehrlichiosis ehrlichiosis NN 367 369 in in IN 370 373 the the DT 374 380 United United NNP 381 387 States State NNPS 387 388 . . . 389 392 Our our PRP$ 393 401 previous previous JJ 402 409 studies study NNS 410 416 showed show VBD 417 421 that that IN 422 425 the the DT 426 434 exposure exposure NN 435 437 of of IN 438 443 human human JJ 444 453 monocytes monocyte NNS 454 456 to to TO 457 459 E. e. FW 460 471 chaffeensis chaffeensis FW 472 479 induces induce VBZ 480 483 the the DT 484 494 expression expression NN 495 497 of of IN 498 515 interleukin-1beta interleukin-1beta NN 516 517 ( ( ( 517 525 IL-1beta IL-1beta NNP 525 526 ) ) ) 526 527 , , , 528 532 IL-8 il-8 NN 532 533 , , , 534 537 and and CC 538 543 IL-10 il-10 NN 544 549 genes gene NNS 550 552 in in FW 553 558 vitro vitro FW 559 562 but but CC 563 566 not not RB 567 570 the the DT 571 581 expression expression NN 582 584 of of IN 585 590 tumor tumor NN 591 599 necrosis necrosis NN 600 606 factor factor NN 607 612 alpha alpha NN 613 614 ( ( ( 614 623 TNF-alpha TNF-alpha NNP 623 624 ) ) ) 625 628 and and CC 629 633 IL-6 IL-6 NNP 634 639 mRNAs mrna NNS 639 640 . . . 641 643 In in IN 644 648 this this DT 649 654 study study NN 654 655 , , , 656 659 the the DT 660 666 effect effect NN 667 669 of of IN 670 677 anti-E. anti-e. FW 678 689 chaffeensis chaffeensis FW 690 698 antibody antibody NN 699 708 complexed complexe VBN 709 713 with with IN 714 716 E. e. FW 717 728 chaffeensis chaffeensis FW 729 731 on on IN 732 735 the the DT 736 746 expression expression NN 747 749 of of IN 750 755 major major JJ 756 771 proinflammatory proinflammatory JJ 772 781 cytokines cytokine NNS 782 784 in in IN 785 790 human human JJ 791 800 monocytes monocyte NNS 801 804 was be VBD 805 813 examined examine VBN 813 814 . . . 815 820 Human human JJ 821 830 monocytic monocytic JJ 831 835 cell cell NN 836 840 line line NN 841 846 THP-1 thp-1 NN 847 850 was be VBD 851 858 treated treat VBN 859 863 with with IN 864 866 E. e. FW 867 878 chaffeensis chaffeensis FW 879 884 which which WDT 885 888 had have VBD 889 893 been be VBN 894 906 preincubated preincubate VBN 907 911 with with IN 912 917 human human JJ 918 925 anti-E. anti-e. FW 926 937 chaffeensis chaffeensis FW 938 943 serum serum NN 944 947 for for IN 948 949 2 2 CD 950 951 h h NN 951 952 , , , 953 956 and and CC 957 960 the the DT 961 967 levels level NNS 968 970 of of IN 971 979 cytokine cytokine NN 980 985 mRNAs mrna NNS 986 990 were be VBD 991 1000 evaluated evaluate VBN 1001 1003 by by IN 1004 1015 competitive competitive JJ 1016 1023 reverse reverse JJ 1024 1041 transcription-PCR transcription-PCR NNP 1041 1042 . . . 1043 1050 Anti-E. anti-e. FW 1051 1062 chaffeensis chaffeensis FW 1063 1071 antibody antibody NN 1072 1081 complexed complexe VBN 1082 1086 with with IN 1087 1089 E. e. FW 1090 1101 chaffeensis chaffeensis FW 1102 1115 significantly significantly RB 1116 1124 enhanced enhance VBD 1125 1129 mRNA mrna NN 1130 1140 expression expression NN 1141 1143 of of IN 1144 1152 IL-1beta IL-1beta NNP 1153 1155 in in IN 1156 1161 THP-1 thp-1 NN 1162 1167 cells cell NNS 1167 1168 . . . 1169 1172 The the DT 1173 1183 expression expression NN 1184 1186 of of IN 1187 1196 TNF-alpha TNF-alpha NNP 1197 1200 and and CC 1201 1205 IL-6 IL-6 NNP 1206 1211 mRNAs mrna NNS 1212 1215 was be VBD 1216 1220 also also RB 1221 1228 induced induce VBN 1228 1229 . . . 1230 1233 The the DT 1234 1240 levels level NNS 1241 1243 of of IN 1244 1252 secreted secrete VBN 1253 1261 IL-1beta IL-1beta NNP 1261 1262 , , , 1263 1272 TNF-alpha TNF-alpha NNP 1272 1273 , , , 1274 1277 and and CC 1278 1282 IL-6 il-6 NN 1283 1289 during during IN 1290 1292 24 24 CD 1293 1294 h h NN 1295 1297 of of IN 1298 1309 stimulation stimulation NN 1310 1314 were be VBD 1315 1325 comparable comparable JJ 1326 1328 to to TO 1329 1334 those those DT 1335 1342 induced induce VBN 1343 1345 by by IN 1346 1357 Escherichia escherichia FW 1358 1362 coli coli FW 1363 1381 lipopolysaccharide lipopolysaccharide NN 1382 1384 at at IN 1385 1386 1 1 CD 1387 1397 microg/ml. microg/ml. NN 1398 1401 Fab Fab NNP 1402 1410 fragment fragment NN 1411 1413 of of IN 1414 1421 anti-E. anti-e. FW 1422 1433 chaffeensis chaffeensis FW 1434 1448 immunoglobulin immunoglobulin NN 1449 1450 G G NNP 1451 1460 complexed complexe VBN 1461 1465 with with IN 1466 1468 E. e. FW 1469 1480 chaffeensis chaffeensis FW 1481 1484 did do VBD 1485 1488 not not RB 1489 1495 induce induce VB 1496 1499 any any DT 1500 1502 of of IN 1503 1508 these these DT 1509 1514 three three CD 1515 1524 cytokines cytokine NNS 1524 1525 , , , 1526 1536 indicating indicate VBG 1537 1541 that that IN 1542 1552 ehrlichial ehrlichial JJ 1553 1560 binding binding NN 1561 1563 is be VBZ 1564 1572 required require VBN 1573 1576 for for IN 1577 1585 IL-1beta IL-1beta NNP 1586 1590 mRNA mRNA NNP 1591 1601 expression expression NN 1602 1605 and and CC 1606 1610 that that IN 1611 1618 binding binding NN 1619 1621 of of IN 1622 1625 the the DT 1626 1632 immune immune JJ 1633 1640 complex complex NN 1641 1643 to to TO 1644 1647 the the DT 1648 1650 Fc Fc NNP 1651 1656 gamma gamma NN 1657 1665 receptor receptor NN 1666 1668 is be VBZ 1669 1677 required require VBN 1678 1681 for for IN 1682 1691 TNF-alpha TNF-alpha NNP 1692 1695 and and CC 1696 1700 IL-6 IL-6 NNP 1701 1705 mRNA mRNA NNP 1706 1716 expression expression NN 1717 1720 and and CC 1721 1729 enhanced enhance VBN 1730 1738 IL-1beta IL-1beta NNP 1739 1743 mRNA mrna NN 1744 1754 expression expression NN 1754 1755 . . . 1756 1767 Furthermore furthermore RB 1767 1768 , , , 1769 1778 prolonged prolonged JJ 1779 1790 degradation degradation NN 1791 1793 of of IN 1794 1807 IkappaB-alpha IkappaB-alpha NNP 1808 1811 and and CC 1812 1822 activation activation NN 1823 1825 of of IN 1826 1835 NF-kappaB NF-kappaB NNP 1836 1840 were be VBD 1841 1853 demonstrated demonstrate VBN 1854 1856 in in IN 1857 1862 THP-1 thp-1 NN 1863 1868 cells cell NNS 1869 1876 exposed expose VBN 1877 1879 to to TO 1880 1887 anti-E. anti-e. FW 1888 1899 chaffeensis chaffeensis FW 1900 1905 serum serum NN 1906 1909 and and CC 1910 1912 E. e. FW 1913 1924 chaffeensis chaffeensis FW 1924 1925 . . . 1926 1930 This this DT 1931 1937 result result NN 1938 1945 implies imply VBZ 1946 1950 that that IN 1951 1962 development development NN 1963 1965 of of IN 1966 1973 anti-E. anti-e. FW 1974 1985 chaffeensis chaffeensis FW 1986 1994 antibody antibody NN 1995 1997 in in IN 1998 2006 patients patient NNS 2007 2010 can can MD 2011 2017 result result VB 2018 2020 in in IN 2021 2024 the the DT 2025 2035 production production NN 2036 2038 of of IN 2039 2044 major major JJ 2045 2060 proinflammatory proinflammatory JJ 2061 2070 cytokines cytokine NNS 2070 2071 , , , 2072 2077 which which WDT 2078 2081 may may MD 2082 2086 play play VB 2087 2089 an an DT 2090 2099 important important JJ 2100 2104 role role NN 2105 2107 in in IN 2108 2111 the the DT 2112 2127 pathophysiology pathophysiology NN 2128 2130 of of IN 2131 2143 ehrlichiosis ehrlichiosis NN 2144 2147 and and CC 2148 2154 immune immune JJ 2155 2164 responses response NNS 2165 2167 to to TO 2168 2170 it it PRP 2170 2171 . . .