0 10 Epithelial epithelial JJ 11 25 cell-initiated cell-initiated JJ 26 38 inflammation inflammation NN 39 44 plays play VBZ 45 46 a a DT 47 54 crucial crucial JJ 55 59 role role NN 60 62 in in IN 63 68 early early JJ 69 75 tissue tissue NN 76 82 damage damage NN 83 85 in in IN 86 92 amebic amebic JJ 93 102 infection infection NN 103 105 of of IN 106 111 human human JJ 112 121 intestine intestine NN 121 122 . . . 124 134 BACKGROUND background NN 135 136 & & CC 137 141 AIMS AIMS NNP 141 142 : : : 143 152 Entamoeba Entamoeba NNP 153 164 histolytica histolytica NN 165 174 infection infection NN 175 177 of of IN 178 181 the the DT 182 191 intestine intestine NN 192 195 can can MD 196 202 induce induce VB 203 209 severe severe JJ 210 213 gut gut NN 214 226 inflammation inflammation NN 226 227 . . . 228 231 The the DT 232 236 aims aim NNS 237 239 of of IN 240 244 this this DT 245 250 study study NN 251 255 were be VBD 256 258 to to TO 259 265 assess assess VB 266 269 the the DT 270 274 role role NN 275 277 of of IN 278 281 the the DT 282 286 host host NN 287 299 inflammatory inflammatory JJ 300 308 response response NN 309 311 in in IN 312 315 the the DT 316 322 tissue tissue NN 323 329 damage damage NN 330 338 observed observe VBN 339 343 with with IN 344 353 amebiasis amebiasis NN 354 357 and and CC 358 361 the the DT 362 366 role role NN 367 369 of of IN 370 373 the the DT 374 384 intestinal intestinal JJ 385 395 epithelial epithelial JJ 396 400 cell cell NN 401 403 in in IN 404 414 initiating initiate VBG 415 419 that that DT 420 428 response response NN 428 429 . . . 430 437 METHODS methods NNS 437 438 : : : 439 441 E. e. FW 442 453 histolytica histolytica NN 454 463 infection infection NN 464 467 was be VBD 468 479 established establish VBN 480 482 in in IN 483 488 human human JJ 489 499 intestinal intestinal JJ 500 510 xenografts xenograft NNS 511 513 in in IN 514 520 severe severe JJ 521 529 combined combined JJ 530 545 immunodeficient immunodeficient JJ 546 547 ( ( ( 547 558 SCID-HU-INT scid-hu-int JJ 558 559 ) ) ) 560 564 mice mouse NNS 564 565 . . . 566 571 Human human JJ 572 582 intestinal intestinal JJ 583 593 epithelial epithelial JJ 594 598 cell cell NN 599 611 inflammatory inflammatory JJ 612 621 responses response NNS 622 624 to to TO 625 631 amebic amebic JJ 632 641 infection infection NN 642 646 were be VBD 647 656 inhibited inhibit VBN 657 659 by by IN 660 663 the the DT 664 676 intraluminal intraluminal JJ 677 691 administration administration NN 692 694 of of IN 695 697 an an DT 698 707 antisense antisense JJ 708 723 oligonucleotide oligonucleotide NN 724 726 to to TO 727 730 the the DT 731 736 human human JJ 737 740 p65 p65 NN 741 748 subunit subunit NN 749 751 of of IN 752 759 nuclear nuclear JJ 760 766 factor factor NN 767 773 kappaB kappab NN 773 774 , , , 775 778 and and CC 779 782 the the DT 783 787 role role NN 788 790 of of IN 791 802 neutrophils neutrophil NNS 803 805 in in IN 806 812 tissue tissue NN 813 819 damage damage NN 820 828 observed observe VBN 829 833 with with IN 834 843 amebiasis amebiasis NN 844 847 was be VBD 848 855 studied study VBN 856 858 by by IN 859 868 depleting deplete VBG 869 880 neutrophils neutrophil NNS 881 885 from from IN 886 897 SCID-HU-INT scid-hu-int JJ 898 902 mice mouse NNS 902 903 . . . 904 911 RESULTS results NNS 911 912 : : : 913 927 Administration Administration NNP 928 930 of of IN 931 934 the the DT 935 944 antisense antisense JJ 945 960 oligonucleotide oligonucleotide NN 961 968 blocked block VBD 969 972 the the DT 973 983 production production NN 984 986 of of IN 987 992 human human JJ 993 1004 interleukin interleukin NN 1005 1010 1beta 1beta NN 1011 1014 and and CC 1015 1026 interleukin interleukin NN 1027 1028 8 8 CD 1029 1031 by by IN 1032 1042 intestinal intestinal JJ 1043 1053 epithelial epithelial JJ 1054 1059 cells cell NNS 1060 1063 and and CC 1064 1073 inhibited inhibit VBD 1074 1084 neutrophil neutrophil NN 1085 1091 influx influx NN 1092 1096 into into IN 1097 1100 the the DT 1101 1103 E. E. NNP 1104 1124 histolytica-infected histolytica-infected JJ 1125 1135 intestinal intestinal JJ 1136 1146 xenografts xenograft NNS 1146 1147 . . . 1148 1158 Inhibition Inhibition NNP 1159 1161 of of IN 1162 1165 the the DT 1166 1169 gut gut NN 1170 1182 inflammatory inflammatory JJ 1183 1191 response response NN 1192 1194 by by IN 1195 1198 the the DT 1199 1208 antisense antisense JJ 1209 1224 oligonucleotide oligonucleotide NN 1225 1227 or or CC 1228 1231 the the DT 1232 1241 depletion depletion NN 1242 1244 of of IN 1245 1256 neutrophils neutrophil NNS 1257 1261 from from IN 1262 1270 SCID-HU- scid-hu- NN 1271 1274 INT INT NNP 1275 1279 mice mouse NNS 1280 1287 blocked block VBD 1288 1291 the the DT 1292 1300 increase increase NN 1301 1303 in in IN 1304 1314 intestinal intestinal JJ 1315 1327 permeability permeability NN 1328 1336 observed observe VBN 1337 1341 with with IN 1342 1348 amebic amebic JJ 1349 1358 infection infection NN 1358 1359 . . . 1360 1371 CONCLUSIONS conclusions NNS 1371 1372 : : : 1373 1383 Intestinal intestinal JJ 1384 1394 epithelial epithelial JJ 1395 1400 cells cell NNS 1401 1409 initiate initiate VBP 1410 1412 an an DT 1413 1425 inflammatory inflammatory JJ 1426 1434 response response NN 1435 1439 with with IN 1440 1449 resulting result VBG 1450 1469 neutrophil-mediated neutrophil-mediated JJ 1470 1476 tissue tissue NN 1477 1483 damage damage NN 1484 1486 in in IN 1487 1495 response response NN 1496 1498 to to TO 1499 1501 E. e. FW 1502 1513 histolytica histolytica NN 1514 1523 infection infection NN 1523 1524 ; ; : 1525 1529 this this DT 1530 1542 inflammatory inflammatory JJ 1543 1550 cascade cascade NN 1551 1554 can can MD 1555 1557 be be VB 1558 1565 blocked block VBN 1566 1568 by by IN 1569 1579 inhibiting inhibit VBG 1580 1583 the the DT 1584 1597 transcription transcription NN 1598 1600 of of IN 1601 1606 genes gene NNS 1607 1616 regulated regulate VBN 1617 1619 by by IN 1620 1627 nuclear nuclear JJ 1628 1634 factor factor NN 1635 1641 kappaB kappab NN 1641 1642 . . .