0 19 Cytokine-modulating cytokine-modulating JJ 20 28 activity activity NN 29 31 of of IN 32 41 tepoxalin tepoxalin NN 41 42 , , , 43 44 a a DT 45 48 new new JJ 49 58 potential potential NN 59 72 antirheumatic antirheumatic JJ 72 73 . . . 75 84 Tepoxalin Tepoxalin NNP 85 87 is be VBZ 88 89 a a DT 90 93 new new JJ 94 98 dual dual JJ 99 128 cyclooxygenase/5-lipoxygenase cyclooxygenase/5-lipoxygenase NN 129 146 anti-inflammatory anti-inflammatory JJ 147 155 compound compound NN 156 165 currently currently RB 166 171 under under IN 172 180 clinical clinical JJ 181 194 investigation investigation NN 194 195 . . . 196 198 It it PRP 199 202 has have VBZ 203 207 been be VBN 208 213 shown show VBN 214 216 to to TO 217 224 possess possess VB 225 242 anti-inflammatory anti-inflammatory JJ 243 251 activity activity NN 252 254 in in IN 255 256 a a DT 257 264 variety variety NN 265 267 of of IN 268 274 animal animal NN 275 281 models model NNS 282 285 and and CC 286 290 more more RBR 291 299 recently recently RB 300 302 to to TO 303 310 inhibit inhibit VB 311 315 IL-2 il-2 NN 316 323 induced induced JJ 324 330 signal signal NN 331 343 transduction transduction NN 343 344 . . . 345 348 The the DT 349 356 current current JJ 357 362 study study NN 363 366 was be VBD 367 376 conducted conduct VBN 377 379 to to TO 380 388 evaluate evaluate VB 389 392 the the DT 393 401 cytokine cytokine NN 402 412 modulating modulating NN 413 421 activity activity NN 422 424 of of IN 425 434 tepoxalin tepoxalin NN 435 438 and and CC 439 442 the the DT 443 447 role role NN 448 450 of of IN 451 455 iron iron NN 456 458 in in IN 459 464 these these DT 465 472 effects effect NNS 472 473 . . . 474 476 In in IN 477 482 human human JJ 483 493 peripheral peripheral JJ 494 499 blood blood NN 500 511 mononuclear mononuclear JJ 512 517 cells cell NNS 518 519 ( ( ( 519 523 PBMC PBMC NNP 523 524 ) ) ) 525 535 stimulated stimulate VBN 536 540 with with IN 541 549 OKT3/PMA OKT3/PMA NNP 549 550 , , , 551 560 tepoxalin tepoxalin NN 561 570 inhibited inhibit VBD 571 581 lymphocyte lymphocyte NN 582 595 proliferation proliferation NN 596 600 with with IN 601 603 an an DT 604 608 IC50 ic50 NN 609 611 of of IN 612 613 6 6 CD 614 620 microM microm NN 620 621 . . . 622 634 Additionally additionally RB 634 635 , , , 636 638 it it PRP 639 648 inhibited inhibit VBD 649 652 the the DT 653 663 production production NN 664 666 of of IN 667 671 LTB4 ltb4 NN 672 673 ( ( ( 673 677 IC50 ic50 NN 678 679 = = SYM 680 683 0.5 0.5 CD 684 690 microM microM NNP 690 691 ) ) ) 692 695 and and CC 696 699 the the DT 700 709 cytokines cytokine NNS 710 714 IL-2 il-2 NN 714 715 , , , 716 720 IL-6 IL-6 NNP 721 724 and and CC 725 728 TNF TNF NNP 729 734 alpha alpha SYM 735 736 ( ( ( 736 740 IC50 ic50 NN 741 742 = = SYM 743 748 10-12 10-12 CD 749 755 microM microM NNP 755 756 ) ) ) 756 757 . . . 758 770 Cytotoxicity Cytotoxicity NNP 771 774 was be VBD 775 778 not not RB 779 791 demonstrated demonstrate VBN 792 794 at at IN 795 800 these these DT 801 815 concentrations concentration NNS 815 816 . . . 817 825 Add-back add-back JJ 826 837 experiments experiment NNS 838 842 with with IN 843 849 either either CC 850 859 cytokines cytokine NNS 860 861 ( ( ( 861 865 IL-2 IL-2 NNP 866 868 or or CC 869 873 IL-6 IL-6 NNP 873 874 ) ) ) 874 875 , , , 876 880 LTB4 ltb4 NN 881 883 or or CC 884 895 conditioned condition VBN 896 901 media medium NNS 902 908 failed fail VBD 909 911 to to TO 912 919 restore restore VB 920 923 the the DT 924 937 proliferative proliferative JJ 938 946 response response NN 947 949 in in IN 950 953 the the DT 954 962 presence presence NN 963 965 of of IN 966 975 tepoxalin tepoxalin NN 975 976 . . . 977 984 However however RB 984 985 , , , 986 989 the the DT 990 1000 concurrent concurrent JJ 1001 1009 addition addition NN 1010 1012 of of IN 1013 1017 iron iron NN 1018 1019 ( ( ( 1019 1021 in in IN 1022 1025 the the DT 1026 1030 form form NN 1031 1033 of of IN 1034 1041 ferrous ferrous JJ 1042 1044 or or CC 1045 1051 ferric ferric JJ 1052 1060 chloride chloride NN 1061 1064 and and CC 1065 1070 other other JJ 1071 1075 iron iron NN 1076 1081 salts salt NNS 1081 1082 ) ) ) 1083 1091 reversed reverse VBD 1092 1095 the the DT 1096 1106 inhibition inhibition NN 1107 1109 of of IN 1110 1123 proliferation proliferation NN 1124 1130 caused cause VBN 1131 1133 by by IN 1134 1143 tepoxalin tepoxalin NN 1143 1144 . . . 1145 1154 Tepoxalin Tepoxalin NNP 1155 1159 also also RB 1160 1168 inhibits inhibit VBZ 1169 1172 the the DT 1173 1183 activation activation NN 1184 1186 of of IN 1187 1189 NF NF NNP 1190 1195 kappa kappa NN 1196 1197 B B NNP 1197 1198 , , , 1199 1200 a a DT 1201 1214 transcription transcription NN 1215 1221 factor factor NN 1222 1227 which which WDT 1228 1232 acts act VBZ 1233 1235 on on IN 1236 1243 several several JJ 1244 1252 cytokine cytokine NN 1253 1258 genes gene NNS 1258 1259 . . . 1260 1269 Tepoxalin Tepoxalin NNP 1269 1271 ’s 's POS 1272 1278 effect effect NN 1279 1281 on on IN 1282 1284 NF NF NNP 1285 1290 kappa kappa NN 1291 1292 B B NNP 1293 1295 is be VBZ 1296 1300 also also RB 1301 1309 reversed reverse VBN 1310 1312 by by IN 1313 1316 the the DT 1317 1325 addition addition NN 1326 1328 of of IN 1329 1333 iron iron NN 1334 1339 salts salt NNS 1339 1340 . . . 1341 1346 These these DT 1347 1351 data datum NNS 1352 1359 suggest suggest VBP 1360 1364 that that IN 1365 1368 the the DT 1369 1375 action action NN 1376 1378 of of IN 1379 1388 tepoxalin tepoxalin NN 1389 1391 to to TO 1392 1399 inhibit inhibit VB 1400 1413 proliferation proliferation NN 1414 1416 in in IN 1417 1421 PBMC PBMC NNP 1422 1425 may may MD 1426 1428 be be VB 1429 1431 at at IN 1432 1437 least least JJS 1438 1440 in in IN 1441 1445 part part NN 1446 1449 due due JJ 1450 1452 to to TO 1453 1456 its its PRP$ 1457 1464 ability ability NN 1465 1467 to to TO 1468 1474 reduce reduce VB 1475 1478 the the DT 1479 1485 amount amount NN 1486 1488 of of IN 1489 1498 available available JJ 1499 1503 iron iron NN 1504 1513 resulting result VBG 1514 1516 in in IN 1517 1526 decreased decrease VBN 1527 1537 activation activation NN 1538 1540 of of IN 1541 1543 NF NF NNP 1544 1549 kappa kappa NN 1550 1551 B B NNP 1552 1555 and and CC 1556 1566 subsequent subsequent JJ 1567 1577 inhibition inhibition NN 1578 1580 of of IN 1581 1589 cytokine cytokine NN 1590 1600 production production NN 1600 1601 . . .