0 10 Inhibition Inhibition NNP 11 13 of of IN 14 30 cyclooxygenase-2 cyclooxygenase-2 NN 31 41 expression expression NN 42 44 by by IN 45 62 4-trifluoromethyl 4-trifluoromethyl NN 63 74 derivatives derivative NNS 75 77 of of IN 78 88 salicylate salicylate NN 88 89 , , , 90 99 triflusal triflusal NN 99 100 , , , 101 104 and and CC 105 108 its its PRP$ 109 121 deacetylated deacetylate VBN 122 132 metabolite metabolite NN 132 133 , , , 134 168 2-hydroxy-4-trifluoromethylbenzoic 2-hydroxy-4-trifluoromethylbenzoic JJ 169 173 acid acid NN 173 174 . . . 176 179 The the DT 180 191 therapeutic therapeutic JJ 192 201 potential potential NN 202 204 of of IN 205 210 drugs drug NNS 211 215 that that WDT 216 221 block block VBP 222 225 the the DT 226 235 induction induction NN 236 238 of of IN 239 255 cyclooxygenase-2 cyclooxygenase-2 NN 256 259 has have VBZ 260 264 been be VBN 265 275 emphasized emphasize VBN 275 276 . . . 277 281 When when WRB 282 285 two two CD 286 303 4-trifluoromethyl 4-trifluoromethyl NN 304 314 salicylate salicylate NN 315 326 derivatives derivative NNS 327 328 [ [ ( 328 363 2-acetoxy-4-trifluoromethyl-benzoic 2-acetoxy-4-trifluoromethyl-benzoic JJ 364 368 acid acid NN 369 370 ( ( ( 370 379 triflusal triflusal NN 379 380 ) ) ) 381 384 and and CC 385 388 its its PRP$ 389 401 deacetylated deacetylate VBN 402 412 metabolite metabolite NN 413 447 2-hydroxy-4-trifluoromethylbenzoic 2-hydroxy-4-trifluoromethylbenzoic JJ 448 452 acid acid NN 453 454 ( ( ( 454 457 HTB HTB NNP 457 458 ) ) ) 458 459 ] ] ) 460 464 were be VBD 465 473 compared compare VBN 474 478 with with IN 479 486 aspirin aspirin NN 487 490 and and CC 491 497 sodium sodium NN 498 508 salicylate salicylate NN 509 511 as as IN 512 528 cyclooxygenase-2 cyclooxygenase-2 NN 529 530 ( ( ( 530 535 COX-2 cox-2 NN 535 536 ) ) ) 537 547 inhibitors inhibitor NNS 547 548 , , , 549 551 we we PRP 552 560 observed observe VBD 561 565 that that IN 566 568 in in IN 569 578 bacterial bacterial JJ 579 607 lipopolysaccharide-activated lipopolysaccharide-activated JJ 608 613 human human JJ 614 619 blood blood NN 619 620 , , , 621 630 triflusal triflusal NN 630 631 , , , 632 639 aspirin aspirin NN 639 640 , , , 641 644 and and CC 645 648 HTB HTB NNP 648 649 , , , 650 653 but but CC 654 657 not not RB 658 664 sodium sodium NN 665 675 salicylate salicylate NN 675 676 , , , 677 686 inhibited inhibit VBD 687 701 COX-2-mediated cox-2-mediated JJ 702 715 prostaglandin prostaglandin NN 716 718 E2 e2 NN 719 720 ( ( ( 720 724 PGE2 pge2 NN 724 725 ) ) ) 726 736 production production NN 737 738 ( ( ( 738 742 IC50 ic50 NN 743 744 = = SYM 745 749 0.16 0.16 CD 749 750 , , , 751 755 0.18 0.18 CD 755 756 , , , 757 761 0.39 0.39 CD 761 762 , , , 763 766 and and CC 767 770 >10 >10 CD 771 773 mM mm NN 773 774 , , , 775 787 respectively respectively RB 787 788 ) ) ) 788 789 . . . 790 797 However however RB 797 798 , , , 799 803 only only RB 804 813 triflusal triflusal NN 814 817 and and CC 818 825 aspirin aspirin NN 826 835 inhibited inhibit VBD 836 844 purified purify VBN 845 850 COX-2 cox-2 NN 851 857 enzyme enzyme NN 857 858 . . . 859 861 To to TO 862 866 test test VB 867 871 this this DT 872 880 apparent apparent JJ 881 892 discrepancy discrepancy NN 892 893 , , , 894 896 we we PRP 897 905 realized realize VBD 906 910 that that IN 911 914 HTB HTB NNP 915 918 and and CC 919 928 triflusal triflusal NN 929 930 ( ( ( 930 933 but but CC 934 941 neither neither CC 942 949 aspirin aspirin NN 950 953 nor nor CC 954 964 salicylate salicylate NN 964 965 ) ) ) 966 974 produced produce VBD 975 976 a a DT 977 1000 concentration-dependent concentration-dependent JJ 1001 1011 inhibition inhibition NN 1012 1014 of of IN 1015 1020 COX-2 cox-2 NN 1021 1028 protein protein NN 1029 1039 expression expression NN 1040 1042 in in IN 1043 1053 peripheral peripheral JJ 1054 1059 human human JJ 1060 1071 mononuclear mononuclear JJ 1072 1077 cells cell NNS 1077 1078 . . . 1079 1083 This this DT 1084 1095 observation observation NN 1096 1099 was be VBD 1100 1107 further further RBR 1108 1117 confirmed confirm VBN 1118 1120 in in IN 1121 1122 a a DT 1123 1126 rat rat NN 1127 1130 air air NN 1131 1136 pouch pouch NN 1137 1142 model model NN 1143 1145 in in FW 1146 1150 vivo vivo FW 1150 1151 , , , 1152 1154 in in IN 1155 1160 which which WDT 1161 1165 both both CC 1166 1173 aspirin aspirin NN 1174 1177 and and CC 1178 1187 triflusal triflusal NN 1188 1197 inhibited inhibit VBD 1198 1202 PGE2 pge2 NN 1203 1213 production production NN 1214 1215 ( ( ( 1215 1219 ID50 id50 NN 1220 1221 = = SYM 1222 1226 18.9 18.9 CD 1227 1230 and and CC 1231 1235 11.4 11.4 CD 1236 1241 mg/kg mg/kg NN 1242 1246 p.o. p.o. NN 1246 1247 , , , 1248 1260 respectively respectively RB 1260 1261 ) ) ) 1262 1265 but but CC 1266 1270 only only RB 1271 1288 triflusal-treated triflusal-treated JJ 1289 1296 animals animal NNS 1297 1303 showed show VBD 1304 1305 a a DT 1306 1314 decrease decrease NN 1315 1317 in in IN 1318 1323 COX-2 cox-2 NN 1324 1334 expression expression NN 1334 1335 . . . 1336 1340 This this DT 1341 1350 different different JJ 1351 1359 behavior behavior NN 1360 1363 may may MD 1364 1366 be be VB 1366 1367 , , , 1368 1370 at at IN 1371 1376 least least JJS 1377 1379 in in IN 1380 1384 part part NN 1384 1385 , , , 1386 1389 due due IN 1390 1392 to to TO 1393 1396 the the DT 1397 1404 ability ability NN 1405 1407 of of IN 1408 1411 HTB HTB NNP 1412 1415 and and CC 1416 1425 triflusal triflusal NN 1426 1428 to to TO 1429 1434 block block VB 1435 1438 the the DT 1439 1449 activation activation NN 1450 1452 of of IN 1453 1456 the the DT 1457 1470 transcription transcription NN 1471 1477 factor factor NN 1478 1485 nuclear nuclear JJ 1486 1499 factor-kappaB factor-kappab NN 1500 1502 to to TO 1503 1504 a a DT 1505 1511 higher high JJR 1512 1518 extent extent NN 1519 1523 than than IN 1524 1531 aspirin aspirin NN 1532 1535 and and CC 1536 1542 sodium sodium NN 1543 1553 salicylate salicylate NN 1553 1554 . . . 1555 1559 Thus thus RB 1559 1560 , , , 1561 1563 in in IN 1564 1572 addition addition NN 1573 1575 to to TO 1576 1586 inhibiting inhibit VBG 1587 1590 the the DT 1591 1596 COX-2 cox-2 NN 1597 1605 activity activity NN 1606 1608 at at IN 1609 1620 therapeutic therapeutic JJ 1621 1635 concentrations concentration NNS 1635 1636 , , , 1637 1646 triflusal triflusal NN 1647 1649 is be VBZ 1650 1654 able able JJ 1655 1657 to to TO 1658 1663 block block VB 1664 1671 through through IN 1672 1675 its its PRP$ 1676 1686 metabolite metabolite NN 1687 1690 HTB htb NN 1691 1694 the the DT 1695 1705 expression expression NN 1706 1708 of of IN 1709 1712 new new JJ 1713 1719 enzyme enzyme NN 1719 1720 , , , 1721 1724 and and CC 1725 1730 hence hence RB 1731 1734 the the DT 1735 1745 resumption resumption NN 1746 1748 of of IN 1749 1753 PGE2 pge2 NN 1754 1763 synthesis synthesis NN 1763 1764 . . . 1765 1774 Triflusal Triflusal NNP 1775 1778 and and CC 1779 1782 HTB HTB NNP 1783 1786 may may MD 1787 1792 exert exert VB 1793 1803 beneficial beneficial JJ 1804 1811 effects effect NNS 1812 1814 in in IN 1815 1824 processes process NNS 1825 1827 in in IN 1828 1833 which which WDT 1834 1836 de de FW 1837 1841 novo novo FW 1842 1847 COX-2 cox-2 NN 1848 1858 expression expression NN 1859 1861 is be VBZ 1862 1870 involved involve VBN 1871 1874 and and CC 1874 1875 , , , 1876 1878 in in IN 1879 1880 a a DT 1881 1888 broader broad JJR 1889 1894 sense sense NN 1894 1895 , , , 1896 1898 in in IN 1899 1911 pathological pathological JJ 1912 1922 situations situation NNS 1923 1925 in in IN 1926 1931 which which WDT 1932 1937 genes gene NNS 1938 1943 under under IN 1944 1951 nuclear nuclear JJ 1952 1965 factor-kappaB factor-kappab NN 1966 1973 control control NN 1974 1977 are be VBP 1978 1990 up-regulated up-regulate VBN 1990 1991 . . .