0 9 Increased increase VBN 10 24 glucocorticoid glucocorticoid NN 25 33 receptor receptor NN 34 38 beta beta NN 39 41 in in IN 42 48 airway airway NN 49 54 cells cell NNS 55 57 of of IN 58 84 glucocorticoid-insensitive glucocorticoid-insensitive JJ 85 91 asthma asthma NN 91 92 . . . 94 108 Glucocorticoid Glucocorticoid NNP 109 110 ( ( ( 110 125 GC)-insensitive gc)-insensitive JJ 126 132 asthma asthma NN 133 135 is be VBZ 136 137 a a DT 138 149 challenging challenging JJ 150 158 clinical clinical JJ 159 166 problem problem NN 167 171 that that WDT 172 175 can can MD 176 178 be be VB 179 189 associated associate VBN 190 194 with with IN 195 211 life-threatening life-threatening JJ 212 219 disease disease NN 220 231 progression progression NN 231 232 . . . 233 236 The the DT 237 246 molecular molecular JJ 247 252 basis basis NN 253 255 of of IN 256 258 GC GC NNP 259 272 insensitivity insensitivity NN 273 275 is be VBZ 276 283 unknown unknown JJ 283 284 . . . 285 296 Alternative alternative JJ 297 305 splicing splicing NN 306 308 of of IN 309 312 the the DT 313 315 GC GC NNP 316 324 receptor receptor NN 325 326 ( ( ( 326 329 GCR GCR NNP 329 330 ) ) ) 331 339 pre-mRNA pre-mRNA NNP 340 349 generates generate VBZ 350 351 a a DT 352 358 second second JJ 359 362 GCR gcr NN 362 363 , , , 364 370 termed term VBN 371 378 GCRbeta GCRbeta NNP 378 379 , , , 380 385 which which WDT 386 390 does do VBZ 391 394 not not RB 395 399 bind bind VB 400 402 GC GC NNP 403 406 but but CC 407 418 antagonizes antagonize VBZ 419 422 the the DT 423 438 transactivating transactivating NN 439 447 activity activity NN 448 450 of of IN 451 454 the the DT 455 462 classic classic JJ 463 466 GCR gcr NN 466 467 . . . 468 472 Thus thus RB 473 482 increased increase VBN 483 493 expression expression NN 494 496 of of IN 497 504 GCRbeta GCRbeta NNP 505 510 could could MD 511 518 account account VB 519 522 for for IN 523 537 glucocorticoid glucocorticoid NN 538 551 insensitivity insensitivity NN 551 552 . . . 553 568 Bronchoalveolar bronchoalveolar JJ 569 575 lavage lavage NN 576 577 ( ( ( 577 580 BAL BAL NNP 580 581 ) ) ) 582 587 cells cell NNS 588 591 and and CC 592 602 peripheral peripheral JJ 603 608 blood blood NN 609 620 mononuclear mononuclear JJ 621 626 cells cell NNS 627 628 ( ( ( 628 632 PBMC PBMC NNP 632 633 ) ) ) 634 638 were be VBD 639 647 examined examine VBN 648 651 for for IN 652 659 GCRbeta GCRbeta NNP 660 676 immunoreactivity immunoreactivity NN 677 682 using use VBG 683 684 a a DT 685 701 GCRbeta-specific gcrbeta-specific JJ 702 710 antibody antibody NN 711 713 by by IN 714 733 immunohistochemical immunohistochemical JJ 734 742 staining staining NN 742 743 . . . 744 748 Cell cell NN 749 761 localization localization NN 762 764 of of IN 765 772 GCRbeta GCRbeta NNP 773 783 expression expression NN 784 787 was be VBD 788 797 performed perform VBN 798 803 using use VBG 804 805 a a DT 806 812 double double JJ 813 827 immunostaining immunostaining NN 828 837 technique technique NN 837 838 . . . 839 847 Patients patient NNS 848 852 with with IN 853 867 GC-insensitive gc-insensitive JJ 868 874 asthma asthma NN 875 884 expressed express VBD 885 886 a a DT 887 900 significantly significantly RB 901 907 higher high JJR 908 914 number number NN 915 917 of of IN 918 940 GCRbeta-immunoreactive gcrbeta-immunoreactive JJ 941 946 cells cell NNS 947 949 in in IN 950 955 their their PRP$ 956 959 BAL bal NN 960 963 and and CC 964 974 peripheral peripheral JJ 975 980 blood blood NN 981 985 than than IN 986 998 GC-sensitive gc-sensitive JJ 999 1009 asthmatics asthmatic NNS 1010 1012 or or CC 1013 1019 normal normal JJ 1020 1027 control control NN 1028 1036 subjects subject NNS 1036 1037 . . . 1038 1049 Furthermore furthermore RB 1049 1050 , , , 1051 1058 GCRbeta GCRbeta NNP 1059 1069 expression expression NN 1070 1072 in in IN 1073 1087 GC-insensitive gc-insensitive JJ 1088 1094 asthma asthma NN 1095 1098 was be VBD 1099 1111 particularly particularly RB 1112 1116 high high JJ 1117 1119 in in IN 1120 1126 airway airway NN 1127 1128 T t NN 1129 1134 cells cell NNS 1134 1135 , , , 1136 1141 which which WDT 1142 1145 are be VBP 1146 1153 thought think VBN 1154 1156 to to TO 1157 1161 play play VB 1162 1163 a a DT 1164 1169 major major JJ 1170 1174 role role NN 1175 1177 in in IN 1178 1181 the the DT 1182 1194 pathogenesis pathogenesis NN 1195 1197 of of IN 1198 1204 asthma asthma NN 1204 1205 . . . 1206 1208 We we PRP 1209 1213 also also RB 1214 1222 examined examine VBD 1223 1226 the the DT 1227 1237 expression expression NN 1238 1240 of of IN 1241 1248 GCRbeta GCRbeta NNP 1249 1251 in in IN 1252 1261 specimens specimen NNS 1262 1266 from from IN 1267 1270 the the DT 1271 1278 airways airway NNS 1279 1281 of of IN 1282 1290 patients patient NNS 1291 1295 with with IN 1296 1303 chronic chronic JJ 1304 1314 bronchitis bronchitis NN 1314 1315 . . . 1316 1318 In in IN 1319 1326 chronic chronic JJ 1327 1337 bronchitis bronchitis NN 1337 1338 , , , 1339 1342 few few JJ 1343 1348 cells cell NNS 1349 1353 were be VBD 1354 1370 GCRbeta-positive gcrbeta-positive JJ 1371 1374 and and CC 1375 1380 their their PRP$ 1381 1388 numbers number NNS 1389 1392 did do VBD 1393 1396 not not RB 1397 1403 differ differ VB 1404 1417 significantly significantly RB 1418 1422 from from IN 1423 1429 normal normal JJ 1430 1437 control control NN 1438 1446 subjects subject NNS 1446 1447 . . . 1448 1450 We we PRP 1451 1459 conclude conclude VBP 1460 1464 that that IN 1465 1479 GC-insensitive gc-insensitive JJ 1480 1486 asthma asthma NN 1487 1489 is be VBZ 1490 1500 associated associate VBN 1501 1505 with with IN 1506 1515 increased increase VBN 1516 1526 expression expression NN 1527 1529 of of IN 1530 1537 GCRbeta GCRbeta NNP 1538 1540 in in IN 1541 1547 airway airway NN 1548 1549 T t NN 1550 1555 cells cell NNS 1555 1556 . . .