0 9 Infection infection NN 10 14 with with IN 15 24 Theileria theileria FW 25 33 annulata annulata FW 34 41 induces induce VBZ 42 52 expression expression NN 53 55 of of IN 56 62 matrix matrix NN 63 80 metalloproteinase metalloproteinase NNP 81 82 9 9 CD 83 86 and and CC 87 100 transcription transcription NN 101 107 factor factor NN 108 112 AP-1 ap-1 NN 113 115 in in IN 116 122 bovine bovine JJ 123 133 leucocytes leucocyte NNS 133 134 . . . 136 145 Theileria theileria FW 146 154 annulata annulata FW 155 162 infects infect VBZ 163 169 bovine bovine JJ 170 180 leucocytes leucocyte NNS 181 184 and and CC 185 192 results result VBZ 193 195 in in IN 196 201 their their PRP$ 202 212 reversible reversible JJ 213 227 transformation transformation NN 228 232 such such IN 233 237 that that IN 238 242 they they PRP 243 249 become become VBP 250 262 immortalised immortalise VBN 263 266 and and CC 267 277 metastatic metastatic JJ 277 278 . . . 279 282 The the DT 283 290 present present JJ 291 296 study study NN 297 306 describes describe VBZ 307 323 parasite-induced parasite-induced JJ 324 331 changes change NNS 332 334 in in IN 335 339 host host NN 340 344 cell cell NN 345 349 gene gene NN 350 360 expression expression NN 361 366 which which WDT 367 371 have have VBP 372 373 a a DT 374 380 direct direct JJ 381 388 bearing bearing NN 389 391 on on IN 392 396 this this DT 397 411 transformation transformation NN 412 419 process process NN 419 420 . . . 421 423 T. t. FW 424 441 annulata-infected annulata-infected JJ 442 452 leucocytes leucocyte NNS 453 460 produce produce VBP 461 462 a a DT 463 469 number number NN 470 472 of of IN 473 478 novel novel JJ 479 496 metalloproteinase metalloproteinase NN 497 507 activities activity NNS 507 508 . . . 509 512 One one CD 513 515 of of IN 516 521 these these DT 521 522 , , , 523 533 previously previously RB 534 540 called call VBN 541 543 B1 b1 NN 543 544 , , , 545 547 is be VBZ 548 549 a a DT 550 556 97-kDa 97-kda JJ 557 564 protein protein NN 565 570 which which WDT 571 573 is be VBZ 574 582 secreted secrete VBN 583 585 in in IN 586 591 large large JJ 592 599 amounts amount NNS 600 603 and and CC 604 607 has have VBZ 608 612 been be VBN 613 621 purified purify VBN 622 626 from from IN 627 639 protein-free protein-free JJ 639 640 , , , 641 652 conditioned conditioned JJ 653 659 medium medium NN 659 660 . . . 661 663 An an DT 664 673 antiserum antiserum NN 674 676 to to TO 677 681 this this DT 682 688 enzyme enzyme NN 689 692 was be VBD 693 697 used use VBN 698 700 to to TO 701 708 isolate isolate VB 709 710 a a DT 711 715 cDNA cdna NN 716 721 clone clone NN 721 722 . . . 723 726 The the DT 727 736 predicted predict VBN 737 744 protein protein NN 745 753 sequence sequence NN 754 756 of of IN 757 759 B1 B1 NNP 760 762 is be VBZ 763 765 81 81 CD 765 766 % % NN 767 776 identical identical JJ 777 779 to to TO 780 785 human human JJ 786 792 matrix matrix NN 793 810 metalloproteinase metalloproteinase NNP 811 812 9 9 CD 813 814 ( ( ( 814 818 MMP9 MMP9 NNP 818 819 ) ) ) 819 820 , , , 821 834 demonstrating demonstrate VBG 835 839 that that IN 840 842 it it PRP 843 845 is be VBZ 846 849 the the DT 850 856 bovine bovine JJ 857 866 homologue homologue NN 867 869 of of IN 870 874 this this DT 875 881 enzyme enzyme NN 881 882 . . . 883 889 RNAase RNAase NNP 890 900 protection protection NN 901 907 assays assay NNS 908 920 demonstrated demonstrate VBD 921 925 that that IN 926 929 the the DT 930 934 MMP9 MMP9 NNP 935 943 activity activity NN 943 944 , , , 945 951 unique unique JJ 952 954 to to TO 955 963 infected infected JJ 964 969 cells cell NNS 969 970 , , , 971 973 is be VBZ 974 977 due due JJ 978 980 to to TO 981 990 increased increase VBN 991 995 MMP9 MMP9 NNP 996 1000 mRNA mrna NN 1001 1007 levels level NNS 1007 1008 . . . 1009 1011 We we PRP 1012 1016 also also RB 1017 1024 assayed assay VBD 1025 1028 the the DT 1029 1035 levels level NNS 1036 1038 of of IN 1039 1052 transcription transcription NN 1053 1059 factor factor NN 1060 1064 AP-1 ap-1 NN 1065 1068 and and CC 1069 1081 demonstrated demonstrate VBD 1082 1086 that that IN 1087 1089 it it PRP 1090 1093 was be VBD 1094 1108 constitutively constitutively RB 1109 1116 present present JJ 1117 1119 in in IN 1120 1129 increased increase VBN 1130 1137 amounts amount NNS 1138 1140 in in IN 1141 1159 Theileria-infected theileria-infected JJ 1160 1165 cells cell NNS 1165 1166 . . . 1167 1169 In in IN 1170 1178 addition addition NN 1179 1181 we we PRP 1182 1189 assayed assay VBD 1190 1193 the the DT 1194 1199 level level NN 1200 1202 of of IN 1203 1207 mRNA mrna NN 1208 1216 encoding encode VBG 1217 1222 c-Fos c-fos NN 1222 1223 , , , 1224 1225 a a DT 1226 1232 common common JJ 1233 1242 component component NN 1243 1245 of of IN 1246 1250 AP-1 ap-1 NN 1251 1254 and and CC 1255 1263 observed observe VBD 1264 1268 that that IN 1269 1271 it it PRP 1272 1275 was be VBD 1276 1282 indeed indeed RB 1283 1295 up-regulated up-regulate VBN 1296 1298 in in IN 1299 1307 infected infected JJ 1308 1313 cells cell NNS 1313 1314 . . . 1315 1320 Since since IN 1321 1325 AP-1 ap-1 NN 1326 1328 is be VBZ 1329 1339 implicated implicate VBN 1340 1342 in in IN 1343 1346 the the DT 1347 1354 control control NN 1355 1357 of of IN 1358 1361 the the DT 1362 1366 cell cell NN 1367 1372 cycle cycle NN 1372 1373 , , , 1374 1377 and and CC 1378 1382 MMP9 MMP9 NNP 1383 1386 can can MD 1387 1393 confer confer VB 1394 1404 metastatic metastatic JJ 1405 1415 properties property NNS 1415 1416 , , , 1417 1422 these these DT 1423 1430 results result NNS 1431 1434 are be VBP 1435 1437 of of IN 1438 1450 considerable considerable JJ 1451 1463 significance significance NN 1464 1468 with with IN 1469 1476 respect respect NN 1477 1479 to to TO 1480 1483 the the DT 1484 1495 transformed transform VBN 1496 1505 phenotype phenotype NN 1506 1513 induced induce VBN 1514 1516 by by IN 1517 1526 Theileria Theileria NNP 1527 1536 infection infection NN 1536 1537 . . .