0 10 Fibroblast Fibroblast NNP 11 17 growth growth NN 18 26 factor-1 factor-1 NN 27 28 ( ( ( 28 33 FGF-1 fgf-1 NN 33 34 ) ) ) 35 43 enhances enhance VBZ 44 48 IL-2 il-2 NN 49 59 production production NN 60 63 and and CC 64 71 nuclear nuclear JJ 72 85 translocation translocation NN 86 88 of of IN 89 98 NF-kappaB NF-kappaB NNP 99 101 in in IN 102 105 FGF FGF NNP 106 122 receptor-bearing receptor-bearing JJ 123 129 Jurkat Jurkat NNP 130 131 T t NN 132 137 cells cell NNS 137 138 . . . 140 150 Fibroblast Fibroblast NNP 151 157 growth growth NN 158 165 factors factor NNS 166 167 ( ( ( 167 171 FGFs FGF NNPS 171 172 ) ) ) 173 176 are be VBP 177 192 heparin-binding heparin-binding JJ 193 201 proteins protein NNS 202 209 crucial crucial JJ 210 212 to to TO 213 226 embryogenesis embryogenesis NN 226 227 , , , 228 240 angiogenesis angiogenesis NN 240 241 , , , 242 245 and and CC 246 251 wound wound NN 252 259 healing healing NN 259 260 . . . 261 266 FGF-1 FGF-1 NNP 267 269 is be VBZ 270 280 abundantly abundantly RB 281 290 expressed express VBN 291 293 in in IN 294 297 the the DT 298 306 synovium synovium NN 307 309 in in IN 310 320 rheumatoid rheumatoid JJ 321 330 arthritis arthritis NN 331 334 and and CC 335 337 in in IN 338 347 rejecting reject VBG 348 358 allografts allograft NNS 358 359 , , , 360 365 sites site NNS 366 368 of of IN 369 376 chronic chronic JJ 377 392 immune-mediated immune-mediated JJ 393 405 inflammation inflammation NN 405 406 . . . 407 410 The the DT 411 420 frequency frequency NN 421 423 of of IN 424 440 FGF-1-responsive fgf-1-responsive JJ 441 442 T t NN 443 448 cells cell NNS 449 451 is be VBZ 452 461 increased increase VBN 462 464 in in IN 465 468 the the DT 469 479 peripheral peripheral JJ 480 485 blood blood NN 486 488 of of IN 489 494 these these DT 495 504 disorders disorder NNS 504 505 , , , 506 509 and and CC 510 511 a a DT 512 516 high high JJ 517 527 percentage percentage NN 528 530 of of IN 531 543 infiltrating infiltrate VBG 544 545 T t NN 546 551 cells cell NNS 552 554 in in IN 555 565 rheumatoid rheumatoid JJ 566 575 arthritis arthritis NN 576 584 synovium synovium NN 585 592 express express VBP 593 602 receptors receptor NNS 603 606 for for IN 607 612 FGF-1 fgf-1 NN 612 613 . . . 614 616 To to TO 617 627 understand understand VB 628 631 the the DT 632 638 action action NN 639 641 of of IN 642 647 FGF-1 fgf-1 NN 648 650 in in IN 651 652 T t NN 653 658 cells cell NNS 658 659 , , , 660 667 studies study NNS 668 672 were be VBD 673 682 initiated initiate VBN 683 685 in in IN 686 692 Jurkat Jurkat NNP 693 694 T t NN 695 700 cells cell NNS 701 705 that that WDT 706 713 express express VBP 714 717 the the DT 718 727 signaling signaling NN 728 735 isoform isoform NN 736 738 of of IN 739 742 FGF FGF NNP 743 753 receptor-1 receptor-1 NN 753 754 . . . 755 760 These these DT 761 772 experiments experiment NNS 773 777 show show VBP 778 782 that that IN 783 788 FGF-1 fgf-1 NN 789 800 stimulation stimulation NN 801 803 of of IN 804 810 Jurkat Jurkat NNP 811 812 T t NN 813 818 cells cell NNS 819 827 provides provide VBZ 828 829 a a DT 830 836 second second JJ 837 843 signal signal NN 844 848 that that WDT 849 857 augments augment VBZ 858 870 TCR-mediated tcr-mediated JJ 871 875 IL-2 il-2 NN 876 886 production production NN 886 887 . . . 888 897 Analogous analogous JJ 898 900 to to TO 901 914 costimulation costimulation NN 915 918 via via IN 919 923 CD28 cd28 NN 923 924 , , , 925 929 this this DT 930 938 activity activity NN 939 941 is be VBZ 942 950 mediated mediate VBN 951 958 through through IN 959 969 activation activation NN 970 972 of of IN 973 983 Rel/kappaB Rel/kappaB NNP 983 984 , , , 985 986 a a DT 987 993 family family NN 994 996 of of IN 997 1010 transcription transcription NN 1011 1018 factors factor NNS 1019 1024 known know VBN 1025 1027 to to TO 1028 1036 regulate regulate VB 1037 1041 IL-2 il-2 NN 1042 1045 and and CC 1046 1051 other other JJ 1052 1072 activation-inducible activation-inducible JJ 1073 1081 proteins protein NNS 1081 1082 . . . 1083 1088 FGF-1 FGF-1 NNP 1089 1094 alone alone RB 1095 1102 induces induce VBZ 1103 1109 modest modest JJ 1110 1117 nuclear nuclear JJ 1118 1131 translocation translocation NN 1132 1134 of of IN 1135 1149 kappaB-binding kappab-binding JJ 1150 1158 proteins protein NNS 1158 1159 , , , 1160 1163 and and CC 1164 1168 this this DT 1169 1182 translocation translocation NN 1183 1185 is be VBZ 1186 1194 enhanced enhance VBN 1195 1197 by by IN 1198 1201 the the DT 1202 1213 combination combination NN 1214 1216 of of IN 1217 1225 anti-CD3 anti-cd3 NN 1226 1229 and and CC 1230 1235 FGF-1 FGF-1 NNP 1235 1236 . . . 1237 1241 This this DT 1242 1251 NF-kappaB NF-kappaB NNP 1252 1259 binding binding NN 1260 1267 complex complex NN 1268 1270 is be VBZ 1271 1279 composed compose VBN 1280 1282 of of IN 1283 1300 transcriptionally transcriptionally RB 1301 1307 active active JJ 1308 1321 p65(RelA)/p50 p65(rela)/p50 NN 1322 1334 heterodimers heterodimer NNS 1335 1338 and and CC 1339 1346 results result NNS 1347 1356 primarily primarily RB 1357 1361 from from IN 1362 1365 the the DT 1366 1374 targeted target VBN 1375 1386 degradation degradation NN 1387 1389 of of IN 1390 1403 IkappaB-alpha IkappaB-alpha NNP 1403 1404 , , , 1405 1407 an an DT 1408 1417 inhibitor inhibitor NN 1418 1422 that that WDT 1423 1433 sequesters sequester VBZ 1434 1444 Rel/kappaB Rel/kappaB NNP 1445 1447 in in IN 1448 1451 the the DT 1452 1461 cytoplasm cytoplasm NN 1461 1462 . . . 1463 1468 These these DT 1469 1473 data datum NNS 1474 1477 are be VBP 1478 1481 the the DT 1482 1487 first first JJ 1488 1490 to to TO 1491 1495 show show VB 1496 1497 a a DT 1498 1508 connection connection NN 1509 1516 between between IN 1517 1522 FGF-1 fgf-1 NN 1523 1532 signaling signaling NN 1533 1536 and and CC 1537 1546 NF-kappaB NF-kappaB NNP 1547 1557 activation activation NN 1558 1565 outside outside IN 1566 1568 of of IN 1569 1578 embryonic embryonic JJ 1579 1590 development development NN 1590 1591 . . . 1592 1595 The the DT 1596 1605 signaling signaling NN 1606 1612 events event NNS 1613 1617 that that WDT 1618 1622 link link VBP 1623 1626 FGF fgf NN 1627 1637 receptor-1 receptor-1 NN 1638 1648 engagement engagement NN 1649 1652 and and CC 1653 1662 NF-kappaB nf-kappab NN 1663 1673 activation activation NN 1674 1676 in in IN 1677 1683 Jurkat Jurkat NNP 1684 1687 are be VBP 1688 1696 probably probably RB 1697 1705 distinct distinct JJ 1706 1710 from from IN 1711 1714 the the DT 1715 1719 CD28 cd28 NN 1720 1733 costimulation costimulation NN 1734 1741 pathway pathway NN 1741 1742 , , , 1743 1748 since since IN 1749 1762 FGF-1-induced fgf-1-induced JJ 1763 1773 Rel/kappaB Rel/kappaB NNP 1774 1781 binding binding NN 1782 1790 proteins protein NNS 1791 1793 do do VBP 1794 1797 not not RB 1798 1805 contain contain VB 1806 1817 significant significant JJ 1818 1824 levels level NNS 1825 1827 of of IN 1828 1833 c-Rel c-rel NN 1834 1837 and and CC 1838 1841 are be VBP 1842 1845 not not RB 1846 1855 identical identical JJ 1856 1860 with with IN 1861 1864 the the DT 1865 1869 CD28 cd28 NN 1870 1878 response response NN 1879 1886 complex complex NN 1886 1887 . . .