0 9 Signaling signaling NN 10 18 pathways pathway NNS 19 27 mediated mediate VBN 28 30 by by IN 31 34 the the DT 35 39 TNF- tnf- NN 40 43 and and CC 44 61 cytokine-receptor cytokine-receptor NN 62 70 families family NNS 71 77 target target VBP 78 79 a a DT 80 86 common common JJ 87 98 cis-element cis-element NN 99 101 of of IN 102 105 the the DT 106 109 IFN IFN NNP 110 120 regulatory regulatory JJ 121 127 factor factor NN 128 129 1 1 CD 130 138 promoter promoter NN 138 139 . . . 141 145 CD40 CD40 NNP 146 156 activation activation NN 157 159 of of IN 160 161 B B NNP 162 167 cells cell NNS 168 170 is be VBZ 171 179 strongly strongly RB 180 190 influenced influence VBN 191 193 by by IN 194 197 the the DT 198 206 presence presence NN 207 209 of of IN 210 219 cytokines cytokine NNS 219 220 . . . 221 228 However however RB 228 229 , , , 230 233 the the DT 234 243 molecular molecular JJ 244 249 basis basis NN 250 253 for for IN 254 257 the the DT 258 267 interplay interplay NN 268 275 between between IN 276 281 these these DT 282 290 distinct distinct JJ 291 298 stimuli stimulus NNS 299 301 is be VBZ 302 305 not not RB 306 313 clearly clearly RB 314 324 delineated delineate VBN 324 325 . . . 326 329 IFN ifn NN 330 340 regulatory regulatory JJ 341 347 factor factor NN 348 349 1 1 CD 350 351 ( ( ( 351 356 IRF-1 irf-1 NN 356 357 ) ) ) 358 360 is be VBZ 361 362 a a DT 363 376 transcription transcription NN 377 383 factor factor NN 384 393 activated activate VBN 394 396 by by IN 397 403 either either CC 404 408 CD40 cd40 NN 409 411 or or CC 412 421 cytokines cytokine NNS 421 422 . . . 423 425 We we PRP 426 430 have have VBP 431 436 found find VBN 437 441 that that IN 442 447 these these DT 448 457 different different JJ 458 462 sets set NNS 463 465 of of IN 466 473 signals signal NNS 474 480 target target VBP 481 482 a a DT 483 489 common common JJ 490 500 cis-acting cis-acting JJ 501 508 element element NN 509 511 in in IN 512 515 the the DT 516 524 promoter promoter NN 525 527 of of IN 528 532 this this DT 533 537 gene gene NN 537 538 , , , 539 542 the the DT 543 548 IRF-1 irf-1 NN 549 564 gamma-activated gamma-activated JJ 565 569 site site NN 570 571 ( ( ( 571 574 GAS GAS NNP 574 575 ) ) ) 575 576 . . . 577 586 Targeting targeting NN 587 589 of of IN 590 593 the the DT 594 599 IRF-1 IRF-1 NNP 600 603 GAS GAS NNP 604 606 is be VBZ 607 610 not not RB 611 619 confined confine VBN 620 622 to to TO 623 633 activation activation NN 634 637 via via IN 638 642 CD40 CD40 NNP 643 646 but but CC 647 654 extends extend VBZ 655 657 to to TO 658 663 other other JJ 664 671 stimuli stimulus NNS 672 676 that that WDT 677 682 mimic mimic VBP 683 686 the the DT 687 691 CD40 cd40 NN 692 701 signaling signaling NN 702 709 cascade cascade NN 709 710 , , , 711 715 like like IN 716 725 TNF-alpha TNF-alpha NNP 726 729 and and CC 730 733 EBV EBV NNP 733 734 . . . 735 737 In in IN 738 746 contrast contrast NN 747 749 to to TO 750 759 induction induction NN 760 762 of of IN 763 768 STATs stat NNS 769 771 by by IN 772 781 cytokines cytokine NNS 781 782 , , , 783 786 the the DT 787 792 IRF-1 irf-1 NN 793 804 GAS-binding gas-binding JJ 805 812 complex complex NN 813 822 activated activate VBN 823 825 by by IN 826 830 CD40 CD40 NNP 830 831 , , , 832 841 TNF-alpha TNF-alpha NNP 841 842 , , , 843 845 or or CC 846 849 EBV EBV NNP 850 858 contains contain VBZ 859 862 Rel Rel NNP 863 871 proteins protein NNS 871 872 , , , 873 885 specifically specifically RB 886 889 p50 p50 NN 890 893 and and CC 894 897 p65 p65 NN 897 898 . . . 899 901 In in IN 902 906 this this DT 907 913 system system NN 913 914 , , , 915 927 simultaneous simultaneous JJ 928 936 exposure exposure NN 937 939 to to TO 940 945 CD40L cd40l NN 946 954 together together RB 955 959 with with IN 960 966 either either CC 967 971 IL-4 il-4 NN 972 974 or or CC 975 984 IFN-gamma IFN-gamma NNP 985 989 does do VBZ 990 993 not not RB 994 998 lead lead VB 999 1001 to to TO 1002 1005 the the DT 1006 1016 activation activation NN 1017 1019 of of IN 1020 1025 novel novel JJ 1026 1034 Rel/STAT rel/stat NN 1035 1044 complexes complex NNS 1044 1045 . . . 1046 1051 Given give VBN 1052 1055 the the DT 1056 1066 importance importance NN 1067 1069 of of IN 1070 1075 IRF-1 irf-1 NN 1076 1078 in in IN 1079 1080 a a DT 1081 1088 variety variety NN 1089 1091 of of IN 1092 1100 biologic biologic JJ 1101 1110 functions function NNS 1111 1115 from from IN 1116 1129 proliferation proliferation NN 1130 1132 to to TO 1133 1142 apoptosis apoptosis NN 1142 1143 , , , 1144 1147 our our PRP$ 1148 1156 findings finding NNS 1157 1164 support support VBP 1165 1168 the the DT 1169 1175 notion notion NN 1176 1180 that that IN 1181 1191 modulation modulation NN 1192 1194 of of IN 1195 1200 IRF-1 irf-1 NN 1201 1207 levels level NNS 1208 1211 may may MD 1212 1214 be be VB 1215 1216 a a DT 1217 1225 critical critical JJ 1226 1233 control control NN 1234 1239 point point NN 1240 1242 in in IN 1243 1244 B B NNP 1245 1249 cell cell NN 1250 1260 activation activation NN 1260 1261 . . .