0 1 A a DT 2 10 negative negative JJ 11 21 regulatory regulatory JJ 22 28 region region NN 29 39 containing contain VBG 40 41 a a DT 42 61 glucocorticosteroid glucocorticosteroid NN 62 70 response response NN 71 78 element element NN 79 80 ( ( ( 80 84 nGRE ngre NN 84 85 ) ) ) 86 88 in in IN 89 92 the the DT 93 98 human human JJ 99 116 interleukin-1beta interleukin-1beta NN 117 121 gene gene NN 121 122 . . . 124 137 Interleukin-1 interleukin-1 NN 138 142 beta beta NN 143 144 ( ( ( 144 152 IL-1beta IL-1beta NNP 152 153 ) ) ) 154 156 is be VBZ 157 160 one one CD 161 163 of of IN 164 167 the the DT 168 172 most most RBS 173 182 important important JJ 183 195 inflammatory inflammatory JJ 196 205 mediators mediator NNS 206 208 in in IN 209 214 human human JJ 215 227 inflammatory inflammatory JJ 228 231 and and CC 232 245 immunological immunological JJ 246 254 diseases disease NNS 254 255 . . . 256 259 The the DT 260 270 regulation regulation NN 271 273 of of IN 274 279 human human JJ 280 288 IL-1beta IL-1beta NNP 289 293 gene gene NN 294 304 expression expression NN 305 308 has have VBZ 309 313 been be VBN 314 321 studied study VBN 322 325 for for IN 326 333 several several JJ 334 339 years year NNS 339 340 , , , 341 344 and and CC 345 346 a a DT 347 350 few few JJ 351 361 regulatory regulatory JJ 362 370 elements element NNS 371 375 have have VBP 376 380 been be VBN 381 391 discovered discover VBN 392 394 in in IN 395 398 the the DT 399 407 promoter promoter NN 408 414 region region NN 414 415 . . . 416 423 However however RB 423 424 , , , 425 431 little little JJ 432 434 is be VBZ 435 440 known know VBN 441 446 about about IN 447 455 negative negative JJ 456 466 regulation regulation NN 467 469 of of IN 470 478 IL-1beta IL-1beta NNP 479 489 expression expression NN 490 492 at at IN 493 496 the the DT 497 512 transcriptional transcriptional JJ 513 518 level level NN 518 519 , , , 520 525 which which WDT 526 529 may may MD 530 534 play play VB 535 537 an an DT 538 547 important important JJ 548 552 role role NN 553 555 in in IN 556 573 anti-inflammatory anti-inflammatory JJ 574 577 and and CC 578 595 immunosuppressive immunosuppressive JJ 596 603 effects effect NNS 603 604 . . . 605 607 We we PRP 608 612 have have VBP 613 623 identified identify VBN 624 625 a a DT 626 634 negative negative JJ 635 645 regulatory regulatory JJ 646 653 element element NN 654 661 located located JJ 662 664 in in IN 665 668 the the DT 669 675 region region NN 676 683 between between IN 684 688 -685 -685 CD 689 692 and and CC 693 697 -395 -395 CD 697 698 . . . 699 705 Within within IN 706 710 this this DT 711 717 region region NN 717 718 , , , 719 720 a a DT 721 726 19-bp 19-bp JJ 727 734 nuclear nuclear JJ 735 741 factor factor NN 742 749 binding binding NN 750 754 site site NN 755 756 ( ( ( 756 760 -570 -570 CD 761 763 to to TO 764 768 -552 -552 CD 768 769 ) ) ) 770 773 was be VBD 774 787 characterized characterize VBN 788 790 by by IN 791 796 DNase DNase NNP 797 798 I i CD 799 811 footprinting footprinting NN 812 815 and and CC 816 831 electromobility electromobility NN 832 837 shift shift NN 838 843 assay assay NN 843 844 . . . 845 846 A a DT 847 856 consensus consensus NN 857 865 sequence sequence NN 866 869 for for IN 870 871 a a DT 872 880 negative negative JJ 881 895 glucocorticoid glucocorticoid NN 896 904 response response NN 905 912 element element NN 913 914 ( ( ( 914 918 nGRE nGRE NNP 918 919 ) ) ) 920 923 and and CC 924 925 a a DT 926 939 transcription transcription NN 940 949 activator activator NN 950 959 protein-2 protein-2 NN 960 967 binding binding NN 968 972 site site NN 973 977 were be VBD 978 983 noted note VBN 984 990 within within IN 991 995 this this DT 996 1005 footprint footprint NN 1005 1006 . . . 1007 1017 Functional functional JJ 1018 1025 studies study NNS 1026 1032 showed show VBD 1033 1034 a a DT 1035 1043 2.5-fold 2.5-fold JJ 1044 1052 increase increase NN 1053 1055 in in IN 1056 1064 promoter promoter NN 1065 1073 activity activity NN 1074 1078 when when WRB 1079 1083 this this DT 1084 1089 19-bp 19-bp JJ 1090 1097 binding binding NN 1098 1102 site site NN 1103 1106 was be VBD 1107 1114 deleted delete VBN 1115 1117 in in IN 1118 1121 the the DT 1122 1130 reporter reporter NN 1131 1141 constructs construct NNS 1142 1154 IL-1beta/CAT IL-1beta/CAT NNP 1155 1158 and and CC 1159 1172 IL-1beta/SV40 IL-1beta/SV40 NNP 1173 1185 promoter/CAT promoter/cat NN 1185 1186 . . . 1187 1200 Dexamethasone Dexamethasone NNP 1201 1202 ( ( ( 1202 1208 10(-8) 10(-8) CD 1209 1210 M M NNP 1210 1211 ) ) ) 1212 1221 repressed repress VBD 1222 1237 chloramphenicol chloramphenicol NN 1238 1255 acetyltransferase acetyltransferase NN 1256 1257 ( ( ( 1257 1260 CAT CAT NNP 1260 1261 ) ) ) 1262 1272 production production NN 1273 1275 by by IN 1276 1278 75 75 CD 1278 1279 % % NN 1280 1282 in in IN 1283 1286 the the DT 1287 1296 wild-type wild-type JJ 1297 1305 fragment fragment NN 1306 1309 but but CC 1310 1313 not not RB 1314 1316 in in IN 1317 1318 a a DT 1319 1327 deletion deletion NN 1328 1334 mutant mutant NN 1335 1342 lacking lack VBG 1343 1346 the the DT 1347 1352 19-bp 19-bp JJ 1353 1357 site site NN 1357 1358 . . . 1359 1360 A a DT 1361 1368 protein protein NN 1369 1371 of of IN 1372 1377 about about RB 1378 1381 150 150 CD 1382 1384 kD kd NN 1385 1389 that that WDT 1390 1395 bound bind VBD 1396 1398 to to TO 1399 1403 this this DT 1404 1412 negative negative JJ 1413 1423 regulatory regulatory JJ 1424 1432 sequence sequence NN 1433 1436 was be VBD 1437 1447 identified identify VBN 1448 1450 by by IN 1451 1453 UV UV NNP 1454 1467 cross-linking cross-linking NN 1467 1468 . . . 1469 1473 This this DT 1474 1476 is be VBZ 1477 1480 the the DT 1481 1486 first first JJ 1487 1498 description description NN 1499 1501 of of IN 1502 1503 a a DT 1504 1512 negative negative JJ 1513 1523 regulatory regulatory JJ 1524 1530 region region NN 1531 1541 responsive responsive JJ 1542 1544 to to TO 1545 1560 glucocorticoids glucocorticoid NNS 1561 1563 in in IN 1564 1565 a a DT 1566 1574 cytokine cytokine NN 1575 1579 gene gene NN 1579 1580 . . .