0 23 Glucocorticoid-mediated glucocorticoid-mediated JJ 24 34 repression repression NN 35 37 of of IN 38 46 cytokine cytokine NN 47 51 gene gene NN 52 65 transcription transcription NN 66 68 in in IN 69 74 human human JJ 75 89 arteritis-SCID arteritis-scid NN 90 98 chimeras chimera NNS 98 99 . . . 101 106 Giant giant JJ 107 111 cell cell NN 112 121 arteritis arteritis NN 122 123 ( ( ( 123 126 GCA GCA NNP 126 127 ) ) ) 128 130 is be VBZ 131 132 a a DT 133 143 vasculitic vasculitic JJ 144 152 syndrome syndrome NN 153 157 that that WDT 158 172 preferentially preferentially RB 173 180 affects affect VBZ 181 187 medium medium NN 188 191 and and CC 192 203 large-sized large-sized JJ 204 212 arteries artery NNS 212 213 . . . 214 228 Glucocorticoid glucocorticoid NN 229 236 therapy therapy NN 237 245 resolves resolve VBZ 246 254 clinical clinical JJ 255 263 symptoms symptom NNS 264 270 within within IN 271 276 hours hour NNS 277 279 to to TO 280 284 days day NNS 284 285 , , , 286 289 but but CC 290 297 therapy therapy NN 298 301 has have VBZ 302 304 to to TO 305 307 be be VB 308 317 continued continue VBN 318 322 over over IN 323 330 several several JJ 331 336 years year NNS 337 339 to to TO 340 347 prevent prevent VB 348 355 disease disease NN 356 364 relapses relapse NNS 364 365 . . . 366 368 It it PRP 369 371 is be VBZ 372 375 not not RB 376 381 known know VBN 382 389 whether whether IN 390 393 and and CC 394 397 how how WRB 398 413 glucocorticoids glucocorticoid NNS 414 420 affect affect VBP 421 424 the the DT 425 433 function function NN 434 436 of of IN 437 440 the the DT 441 453 inflammatory inflammatory JJ 454 464 infiltrate infiltrate NN 465 467 or or CC 468 471 why why WRB 472 475 the the DT 476 483 disease disease NN 484 492 persists persist VBZ 493 506 subclinically subclinically RB 507 514 despite despite IN 515 522 chronic chronic JJ 523 532 treatment treatment NN 532 533 . . . 534 537 GCA GCA NNP 538 540 is be VBZ 541 555 self-sustained self-sustained JJ 556 558 in in IN 559 567 temporal temporal JJ 568 576 arteries artery NNS 577 586 engrafted engraft VBN 587 591 into into IN 592 596 SCID SCID NNP 597 601 mice mouse NNS 601 602 , , , 603 612 providing provide VBG 613 614 a a DT 615 620 model model NN 621 623 in in IN 624 629 which which WDT 630 633 the the DT 634 644 mechanisms mechanism NNS 645 647 of of IN 648 654 action action NN 655 658 and and CC 659 670 limitations limitation NNS 671 673 of of IN 674 688 glucocorticoid glucocorticoid NN 689 696 therapy therapy NN 697 700 can can MD 701 703 be be VB 704 712 examined examine VBN 713 715 in in FW 716 720 vivo vivo FW 720 721 . . . 722 736 Administration Administration NNP 737 739 of of IN 740 753 dexamethasone dexamethasone NN 754 756 to to TO 757 765 temporal temporal JJ 766 777 artery-SCID artery-scid NN 778 786 chimeras chimera NNS 787 790 for for IN 791 792 1 1 CD 793 795 wk wk NN 796 803 induced induce VBD 804 805 a a DT 806 813 partial partial JJ 814 825 suppression suppression NN 826 828 of of IN 829 830 T t NN 831 835 cell cell NN 836 839 and and CC 840 850 macrophage macrophage NN 851 859 function function NN 860 862 as as IN 863 872 indicated indicate VBN 873 875 by by IN 876 879 the the DT 880 887 reduced reduce VBN 888 894 tissue tissue NN 895 909 concentrations concentration NNS 910 912 of of IN 913 917 IL-2 il-2 NN 917 918 , , , 919 927 IL-1beta IL-1beta NNP 927 928 , , , 929 932 and and CC 933 937 IL-6 IL-6 NNP 938 942 mRNA mRNA NNP 942 943 , , , 944 947 and and CC 948 950 by by IN 951 954 the the DT 955 965 diminished diminish VBN 966 976 expression expression NN 977 979 of of IN 980 989 inducible inducible JJ 990 992 NO no NN 993 1001 synthase synthase NN 1001 1002 . . . 1003 1005 In in IN 1006 1014 contrast contrast NN 1014 1015 , , , 1016 1025 synthesis synthesis NN 1026 1028 of of IN 1029 1038 IFN-gamma IFN-gamma NNP 1039 1043 mRNA mRNA NNP 1044 1047 was be VBD 1048 1052 only only RB 1053 1061 slightly slightly RB 1062 1071 decreased decrease VBN 1071 1072 , , , 1073 1076 and and CC 1077 1087 expression expression NN 1088 1090 of of IN 1091 1100 TGF-beta1 TGF-beta1 NNP 1101 1104 was be VBD 1105 1115 unaffected unaffected JJ 1115 1116 . . . 1117 1122 These these DT 1123 1131 findings finding NNS 1132 1142 correlated correlate VBD 1143 1147 with with IN 1148 1158 activation activation NN 1159 1161 of of IN 1162 1165 the the DT 1166 1178 IkappaBalpha IkappaBalpha NNP 1179 1183 gene gene NN 1184 1187 and and CC 1188 1196 blockade blockade NN 1197 1199 of of IN 1200 1203 the the DT 1204 1211 nuclear nuclear JJ 1212 1225 translocation translocation NN 1226 1228 of of IN 1229 1237 NFkappaB NFkappaB NNP 1238 1240 in in IN 1241 1244 the the DT 1245 1261 xenotransplanted xenotransplante VBN 1262 1268 tissue tissue NN 1268 1269 . . . 1270 1283 Dose-response dose-response JJ 1284 1295 experiments experiment NNS 1296 1305 suggested suggest VBD 1306 1310 that that IN 1311 1318 steroid steroid NN 1319 1324 doses dose NNS 1325 1334 currently currently RB 1335 1339 used use VBN 1340 1342 in in IN 1343 1351 clinical clinical JJ 1352 1360 medicine medicine NN 1361 1364 are be VBP 1365 1375 suboptimal suboptimal JJ 1376 1378 in in IN 1379 1389 repressing repress VBG 1390 1407 NFkappaB-mediated nfkappab-mediated JJ 1408 1416 cytokine cytokine NN 1417 1427 production production NN 1428 1430 in in IN 1431 1434 the the DT 1435 1447 inflammatory inflammatory JJ 1448 1455 lesions lesion NNS 1455 1456 . . . 1457 1464 Chronic chronic JJ 1465 1472 steroid steroid NN 1473 1480 therapy therapy NN 1481 1484 was be VBD 1485 1489 able able JJ 1490 1492 to to TO 1493 1500 deplete deplete VB 1501 1504 the the DT 1505 1506 T t NN 1507 1511 cell cell NN 1512 1520 products product NNS 1521 1525 IL-2 IL-2 NNP 1526 1529 and and CC 1530 1539 IFN-gamma IFN-gamma NNP 1539 1540 , , , 1541 1548 whereas whereas IN 1549 1552 the the DT 1553 1563 activation activation NN 1564 1566 of of IN 1567 1586 tissue-infiltrating tissue-infiltrating JJ 1587 1598 macrophages macrophage NNS 1599 1602 was be VBD 1603 1607 only only RB 1608 1617 partially partially RB 1618 1626 affected affect VBN 1626 1627 . . . 1628 1636 IL-1beta IL-1beta NNP 1637 1650 transcription transcription NN 1651 1654 was be VBD 1655 1664 abrogated abrogate VBN 1664 1665 ; ; : 1666 1668 in in IN 1669 1677 contrast contrast NN 1677 1678 , , , 1679 1688 TGF-beta1 TGF-beta1 NNP 1689 1693 mRNA mRNA NNP 1694 1703 synthesis synthesis NN 1704 1707 was be VBD 1708 1715 steroid steroid NN 1716 1725 resistant resistant JJ 1725 1726 . . . 1727 1730 The the DT 1731 1742 persistence persistence NN 1743 1745 of of IN 1746 1768 TGF-beta1-transcribing tgf-beta1-transcribing JJ 1769 1780 macrophages macrophage NNS 1780 1781 , , , 1782 1789 despite despite IN 1790 1799 paralysis paralysis NN 1800 1802 of of IN 1803 1804 T t NN 1805 1809 cell cell NN 1810 1818 function function NN 1818 1819 , , , 1820 1823 may may MD 1824 1831 provide provide VB 1832 1834 an an DT 1835 1846 explanation explanation NN 1847 1850 for for IN 1851 1854 the the DT 1855 1865 chronicity chronicity NN 1866 1868 of of IN 1869 1872 the the DT 1873 1880 disease disease NN 1880 1881 , , , 1882 1885 and and CC 1886 1889 may may MD 1890 1898 identify identify VB 1899 1900 a a DT 1901 1906 novel novel JJ 1907 1918 therapeutic therapeutic JJ 1919 1925 target target NN 1926 1928 in in IN 1929 1933 this this DT 1934 1946 inflammatory inflammatory JJ 1947 1959 vasculopathy vasculopathy NN 1959 1960 . . .