0 9 Decreased decrease VBN 10 15 IL-12 il-12 NN 16 26 production production NN 27 30 and and CC 31 34 Th1 th1 NN 35 39 cell cell NN 40 51 development development NN 52 54 by by IN 55 61 acetyl acetyl NN 62 71 salicylic salicylic JJ 72 85 acid-mediated acid-mediated JJ 86 96 inhibition inhibition NN 97 99 of of IN 100 109 NF-kappaB NF-kappaB NNP 109 110 . . . 112 117 IL-12 il-12 NN 118 120 is be VBZ 121 122 a a DT 123 129 75-kDa 75-kda JJ 130 143 heterodimeric heterodimeric JJ 144 152 cytokine cytokine NN 153 161 composed compose VBN 162 164 of of IN 165 168 two two CD 169 179 covalently covalently RB 180 186 linked link VBN 187 190 p35 p35 NN 191 194 and and CC 195 198 p40 p40 NN 199 205 chains chain NNS 205 206 . . . 207 211 This this DT 212 228 pro-inflammatory pro-inflammatory JJ 229 237 cytokine cytokine NN 238 243 plays play VBZ 244 245 a a DT 246 255 prominent prominent JJ 256 260 role role NN 261 263 in in IN 264 267 the the DT 268 279 development development NN 280 282 of of IN 283 286 Th1 th1 NN 287 300 cell-mediated cell-mediated JJ 301 307 immune immune JJ 308 317 responses response NNS 317 318 . . . 319 322 Th1 th1 NN 323 336 cell-mediated cell-mediated JJ 337 343 immune immune JJ 344 353 responses response NNS 354 358 have have VBP 359 363 been be VBN 364 374 implicated implicate VBN 375 377 in in IN 378 381 the the DT 382 394 pathogenesis pathogenesis NN 395 397 of of IN 398 405 chronic chronic JJ 406 418 inflammatory inflammatory JJ 419 429 autoimmune autoimmune JJ 430 438 diseases disease NNS 438 439 . . . 440 444 Thus thus RB 444 445 , , , 446 451 IL-12 il-12 NN 452 459 appears appear VBZ 460 462 to to TO 463 465 be be VB 466 467 a a DT 468 476 critical critical JJ 477 483 factor factor NN 484 486 in in IN 487 490 the the DT 491 501 generation generation NN 502 505 and and CC 506 517 maintenance maintenance NN 518 520 of of IN 521 528 chronic chronic JJ 529 541 inflammatory inflammatory JJ 542 552 conditions condition NNS 552 553 . . . 554 556 In in IN 557 561 this this DT 562 567 study study NN 567 568 , , , 569 571 we we PRP 572 584 investigated investigate VBD 585 588 the the DT 589 596 effects effect NNS 597 599 of of IN 600 601 a a DT 602 610 commonly commonly RB 611 621 prescribed prescribe VBN 622 639 anti-inflammatory anti-inflammatory JJ 640 644 drug drug NN 644 645 , , , 646 652 acetyl acetyl NN 653 662 salicylic salicylic JJ 663 667 acid acid NN 668 669 ( ( ( 669 672 ASA ASA NNP 672 673 ) ) ) 673 674 , , , 675 677 on on IN 678 683 IL-12 il-12 NN 684 694 production production NN 695 698 and and CC 699 702 Th1 th1 NN 703 707 cell cell NN 708 719 development development NN 719 720 . . . 721 724 ASA ASA NNP 725 728 was be VBD 729 734 found find VBN 735 737 to to TO 738 745 inhibit inhibit VB 746 755 secretion secretion NN 756 758 of of IN 759 762 the the DT 763 768 IL-12 il-12 NN 769 780 heterodimer heterodimer NN 781 783 as as RB 784 788 well well RB 789 791 as as IN 792 795 p40 p40 NN 796 803 monomer monomer NN 804 806 by by IN 807 812 human human JJ 813 822 monocytic monocytic JJ 823 828 cells cell NNS 828 829 . . . 830 834 This this DT 835 838 was be VBD 839 849 associated associate VBN 850 854 with with IN 855 858 the the DT 859 874 down-regulation down-regulation NN 875 877 of of IN 878 886 IL-12p40 IL-12p40 NNP 887 891 mRNA mRNA NNP 892 902 expression expression NN 902 903 . . . 904 912 Analysis Analysis NNP 913 915 of of IN 916 919 the the DT 920 930 regulation regulation NN 931 933 of of IN 934 937 the the DT 938 941 p40 p40 NN 942 946 gene gene NN 947 955 promoter promoter NN 956 964 revealed reveal VBD 965 969 that that IN 970 973 ASA ASA NNP 974 983 inhibited inhibit VBD 984 993 NF-kappaB NF-kappaB NNP 994 1004 activation activation NN 1005 1008 and and CC 1009 1016 binding binding NN 1017 1019 to to TO 1020 1023 the the DT 1024 1034 p40-kappaB p40-kappab NN 1035 1039 site site NN 1040 1042 in in IN 1043 1046 the the DT 1047 1050 p40 p40 NN 1051 1059 promoter promoter NN 1059 1060 , , , 1061 1068 leading lead VBG 1069 1071 to to TO 1072 1087 transcriptional transcriptional JJ 1088 1098 repression repression NN 1099 1101 of of IN 1102 1105 the the DT 1106 1109 p40 p40 NN 1110 1114 gene gene NN 1114 1115 . . . 1116 1124 Addition addition NN 1125 1127 of of IN 1128 1131 ASA ASA NNP 1132 1134 to to TO 1135 1137 an an DT 1138 1140 in in FW 1141 1146 vitro vitro FW 1147 1148 T t NN 1149 1155 helper helper NN 1156 1160 cell cell NN 1161 1176 differentiation differentiation NN 1177 1183 system system NN 1183 1184 , , , 1185 1187 at at IN 1188 1202 concentrations concentration NNS 1203 1213 compatible compatible JJ 1214 1218 with with IN 1219 1225 plasma plasma NN 1226 1232 levels level NNS 1233 1240 reached reach VBN 1241 1247 during during IN 1248 1265 anti-inflammatory anti-inflammatory JJ 1266 1273 therapy therapy NN 1273 1274 , , , 1275 1283 resulted result VBD 1284 1286 in in IN 1287 1294 reduced reduce VBN 1295 1306 development development NN 1307 1309 of of IN 1310 1313 Th1 th1 NN 1314 1319 cells cell NNS 1319 1320 . . . 1321 1326 These these DT 1327 1334 results result NNS 1335 1342 suggest suggest VBP 1343 1347 that that IN 1348 1351 the the DT 1352 1362 inhibition inhibition NN 1363 1365 of of IN 1366 1375 NF-kappaB NF-kappaB NNP 1376 1386 activation activation NN 1387 1389 by by IN 1390 1393 ASA ASA NNP 1394 1399 leads lead VBZ 1400 1402 to to TO 1403 1418 down-regulation down-regulation NN 1419 1421 of of IN 1422 1427 IL-12 il-12 NN 1428 1438 production production NN 1439 1442 and and CC 1443 1453 inhibition inhibition NN 1454 1456 of of IN 1457 1460 Th1 th1 NN 1461 1465 cell cell NN 1466 1477 development development NN 1477 1478 . . .