0 5 Thiol Thiol NNP 6 16 modulation modulation NN 17 25 inhibits inhibit VBZ 26 29 the the DT 30 41 interleukin interleukin NN 42 43 ( ( ( 43 57 IL)-1-mediated il)-1-mediated JJ 58 68 activation activation NN 69 71 of of IN 72 74 an an DT 75 79 IL-1 il-1 NN 80 99 receptor-associated receptor-associated JJ 100 107 protein protein NN 108 114 kinase kinase NNP 115 118 and and CC 119 127 NF-kappa NF-kappa NNP 128 130 B. B. NNP 132 135 The the DT 136 149 interleukin-1 interleukin-1 NN 150 158 receptor receptor NN 159 163 type type NN 164 165 I i CD 166 167 ( ( ( 167 173 IL-1RI IL-1RI NNP 173 174 ) ) ) 175 177 is be VBZ 178 188 associated associate VBN 189 193 with with IN 194 199 other other JJ 200 208 proteins protein NNS 209 213 thus thus RB 214 221 forming form VBG 222 223 a a DT 224 231 complex complex JJ 232 238 system system NN 239 241 by by IN 242 247 which which WDT 248 252 IL-1 il-1 NN 253 259 exerts exert VBZ 260 263 its its PRP$ 264 271 various various JJ 272 279 signals signal NNS 279 280 . . . 281 284 The the DT 285 295 initiating initiate VBG 296 301 event event NN 302 304 is be VBZ 305 310 still still RB 311 320 uncertain uncertain JJ 320 321 , , , 322 325 but but CC 326 336 activation activation NN 337 339 of of IN 340 341 a a DT 342 350 recently recently RB 351 360 described describe VBN 361 380 receptor-associated receptor-associated JJ 381 388 protein protein NN 389 395 kinase kinase NNP 396 398 is be VBZ 399 402 one one CD 403 405 of of IN 406 409 the the DT 410 418 earliest early JJS 419 425 events event NNS 426 436 detectable detectable JJ 437 438 ( ( ( 438 444 Martin Martin NNP 445 447 et et FW 448 451 al. al. FW 451 452 , , , 453 474 Eur.J.Immunol.1994.24 Eur.J.Immunol.1994.24 NNP 474 475 : : : 476 480 1566 1566 CD 480 481 ) ) ) 481 482 . . . 483 487 IL-1 il-1 NN 488 497 signaling signaling NN 498 500 is be VBZ 501 509 commonly commonly RB 510 521 accompanied accompany VBN 522 524 by by IN 525 534 oxidative oxidative JJ 535 544 processes process NNS 545 548 and and CC 549 551 is be VBZ 552 559 thought think VBN 560 562 to to TO 563 565 be be VB 566 573 subject subject JJ 574 576 to to TO 577 582 redox redox NN 583 593 regulation regulation NN 593 594 . . . 595 597 We we PRP 598 607 therefore therefore RB 608 620 investigated investigate VBD 621 628 whether whether IN 629 632 the the DT 633 643 activation activation NN 644 646 of of IN 647 650 the the DT 651 668 IL-1RI-associated il-1ri-associated JJ 669 676 protein protein NN 677 683 kinase kinase NNP 684 689 could could MD 690 692 be be VB 693 694 a a DT 695 701 target target NN 702 705 for for IN 706 711 redox redox NN 712 722 regulation regulation NN 723 726 and and CC 727 734 whether whether IN 735 737 an an DT 738 745 altered altered JJ 746 754 activity activity NN 755 757 of of IN 758 761 the the DT 762 768 kinase kinase NNP 769 774 could could MD 775 784 influence influence VB 785 798 IL-1-mediated il-1-mediated JJ 799 807 NF-kappa NF-kappa NNP 808 809 B B NNP 810 820 activation activation NN 820 821 . . . 822 823 A a DT 824 830 murine murine JJ 831 832 T t NN 833 837 cell cell NN 838 842 line line NN 842 843 , , , 844 847 EL4 EL4 NNP 847 848 , , , 849 852 was be VBD 853 863 stimulated stimulate VBN 864 868 with with IN 869 873 IL-1 il-1 NN 874 878 with with IN 879 882 and and CC 883 890 without without IN 891 903 pretreatment pretreatment NN 904 908 with with IN 909 918 different different JJ 919 928 compounds compound NNS 929 934 known know VBN 935 937 to to TO 938 947 influence influence VB 948 951 the the DT 952 960 cellular cellular JJ 961 966 redox redox NN 967 973 status status NN 973 974 . . . 975 980 Thiol Thiol NNP 981 990 modifying modify VBG 991 997 agents agent NNS 998 1002 like like IN 1003 1010 diamide diamide NN 1010 1011 , , , 1012 1021 menadione menadione NN 1021 1022 , , , 1023 1034 pyrrolidine pyrrolidine NN 1035 1050 dithiocarbamate dithiocarbamate NN 1051 1052 ( ( ( 1052 1056 PDTC PDTC NNP 1056 1057 ) ) ) 1057 1058 , , , 1059 1066 diethyl diethyl NN 1067 1082 dithiocarbamate dithiocarbamate NN 1083 1085 or or CC 1086 1098 phenylarsine phenylarsine NN 1099 1104 oxide oxide NN 1105 1114 inhibited inhibit VBD 1115 1118 the the DT 1119 1131 IL-1-induced il-1-induced JJ 1132 1142 activation activation NN 1143 1145 of of IN 1146 1149 the the DT 1150 1167 IL-1RI-associated il-1ri-associated JJ 1168 1175 protein protein NN 1176 1182 kinase kinase NNP 1182 1183 . . . 1184 1200 N-Acetylcysteine N-Acetylcysteine NNP 1200 1201 , , , 1202 1224 alpha,alpha’-dipyridyl alpha,alpha'-dipyridyl NN 1224 1225 , , , 1226 1239 aminotriazole aminotriazole NN 1240 1242 or or CC 1243 1257 nitrofurantoin nitrofurantoin NN 1258 1261 did do VBD 1262 1265 not not RB 1266 1270 show show VB 1271 1274 any any DT 1275 1281 effect effect NN 1281 1282 . . . 1283 1286 The the DT 1287 1297 inhibition inhibition NN 1298 1300 by by IN 1301 1305 PDTC PDTC NNP 1306 1309 was be VBD 1310 1320 reversible reversible JJ 1321 1327 unless unless IN 1328 1339 glutathione glutathione NN 1340 1349 synthesis synthesis NN 1350 1353 was be VBD 1354 1361 blocked block VBN 1362 1364 by by IN 1365 1375 buthionine buthionine NN 1376 1387 sulfoximine sulfoximine NN 1387 1388 . . . 1389 1392 The the DT 1393 1402 described describe VBN 1403 1413 conditions condition NNS 1414 1419 which which WDT 1420 1429 inhibited inhibit VBD 1430 1432 or or CC 1433 1442 prevented prevent VBD 1443 1446 the the DT 1447 1457 activation activation NN 1458 1460 of of IN 1461 1464 the the DT 1465 1482 IL-1RI-associated il-1ri-associated JJ 1483 1489 kinase kinase NNP 1490 1499 similarly similarly RB 1500 1508 impaired impair VBD 1509 1512 the the DT 1513 1523 activation activation NN 1524 1526 of of IN 1527 1535 NF-kappa NF-kappa NNP 1536 1537 B B NNP 1538 1540 in in IN 1541 1544 EL4 el4 NN 1545 1550 cells cell NNS 1550 1551 . . . 1552 1556 From from IN 1557 1562 these these DT 1563 1575 observations observation NNS 1576 1578 we we PRP 1579 1587 conclude conclude VBP 1588 1592 that that IN 1593 1597 free free JJ 1598 1604 thiols thiol NNS 1605 1607 in in IN 1608 1611 the the DT 1612 1618 IL-1RI IL-1RI NNP 1619 1626 complex complex NN 1627 1630 are be VBP 1631 1640 essential essential JJ 1641 1644 for for IN 1645 1648 the the DT 1649 1659 activation activation NN 1660 1662 of of IN 1663 1666 the the DT 1667 1684 IL-1RI-associated il-1ri-associated JJ 1685 1692 protein protein NN 1693 1699 kinase kinase NNP 1700 1703 and and CC 1704 1708 that that IN 1709 1713 this this DT 1714 1721 process process NN 1722 1724 is be VBZ 1725 1734 mandatory mandatory JJ 1735 1738 for for IN 1739 1743 IL-1 il-1 NN 1744 1753 signaling signaling NN 1754 1761 leading lead VBG 1762 1764 to to TO 1765 1773 NF-kappa NF-kappa NNP 1774 1775 B B NNP 1776 1786 activation activation NN 1786 1787 . . .