0 11 Involvement involvement NN 12 14 of of IN 15 24 adenylate adenylate NN 25 32 cyclase cyclase NN 33 36 and and CC 37 51 p70(S6)-kinase p70(S6)-kinase NNP 52 62 activation activation NN 63 65 in in IN 66 71 IL-10 il-10 NN 72 85 up-regulation up-regulation NN 86 88 in in IN 89 94 human human JJ 95 104 monocytes monocyte NNS 105 107 by by IN 108 112 gp41 gp41 NN 113 121 envelope envelope NN 122 129 protein protein NN 130 132 of of IN 133 138 human human JJ 139 155 immunodeficiency immunodeficiency NN 156 161 virus virus NN 162 166 type type NN 167 168 1 1 CD 168 169 . . . 171 174 Our our PRP$ 175 183 previous previous JJ 184 191 results result NNS 192 196 show show VBP 197 201 that that IN 202 213 recombinant recombinant JJ 214 218 gp41 gp41 NN 219 220 ( ( ( 220 229 aa565-647 aa565-647 NN 229 230 ) ) ) 230 231 , , , 232 235 the the DT 236 249 extracellular extracellular JJ 250 256 domain domain NN 257 259 of of IN 260 265 HIV-1 HIV-1 NNP 266 279 transmembrane transmembrane JJ 280 292 glycoprotein glycoprotein NN 292 293 , , , 294 304 stimulates stimulate VBZ 305 319 interleukin-10 interleukin-10 NN 320 321 ( ( ( 321 326 IL-10 il-10 NN 326 327 ) ) ) 328 338 production production NN 339 341 in in IN 342 347 human human JJ 348 357 monocytes monocyte NNS 357 358 . . . 359 362 The the DT 363 369 signal signal NN 370 377 cascade cascade NN 378 389 transducing transduce VBG 390 394 this this DT 395 401 effect effect NN 402 404 is be VBZ 405 408 not not RB 409 412 yet yet RB 413 418 clear clear JJ 418 419 . . . 420 422 In in IN 423 427 this this DT 428 433 study study NN 433 434 , , , 435 437 we we PRP 438 446 examined examine VBD 447 454 whether whether IN 455 467 gp41-induced gp41-induced JJ 468 473 IL-10 il-10 NN 474 487 up-regulation up-regulation NN 488 490 is be VBZ 491 499 mediated mediate VBN 500 502 by by IN 503 506 the the DT 507 517 previously previously RB 518 527 described describe VBN 528 539 synergistic synergistic JJ 540 550 activation activation NN 551 553 of of IN 554 558 cAMP cAMP NNP 559 562 and and CC 563 572 NF-kappaB NF-kappaB NNP 573 582 pathways. pathways. NN 583 587 gp41 gp41 NN 588 595 induced induce VBD 596 600 cAMP camp NN 601 613 accumulation accumulation NN 614 616 in in IN 617 626 monocytes monocyte NNS 627 629 in in IN 630 631 a a DT 632 637 time- time- NN 638 641 and and CC 642 665 concentration-dependent concentration-dependent JJ 666 672 manner manner NN 673 676 and and CC 677 680 the the DT 681 690 adenylate adenylate NN 691 698 cyclase cyclase NN 699 708 inhibitor inhibitor NN 709 711 SQ SQ NNP 712 717 22536 22536 CD 718 728 suppressed suppress VBD 729 741 gp41-induced gp41-induced JJ 742 747 IL-10 il-10 NN 748 758 production production NN 759 761 in in IN 762 771 monocytes monocyte NNS 771 772 . . . 773 775 In in IN 776 784 contrast contrast NN 784 785 , , , 786 790 gp41 gp41 NN 791 797 failed fail VBD 798 800 to to TO 801 810 stimulate stimulate VB 811 820 NF-kappaB NF-kappaB NNP 821 828 binding binding NN 829 837 activity activity NN 838 840 in in IN 841 843 as as RB 844 848 much much JJ 849 851 as as IN 852 854 no no DT 855 864 NF-kappaB nf-kappab NN 865 870 bound bind VBD 871 873 to to TO 874 877 the the DT 878 882 main main JJ 883 900 NF-kappaB-binding nf-kappab-binding JJ 901 905 site site NN 906 907 2 2 CD 908 910 of of IN 911 914 the the DT 915 920 IL-10 il-10 NN 921 929 promoter promoter NN 930 935 after after IN 936 944 addition addition NN 945 947 of of IN 948 952 gp41 gp41 NN 952 953 . . . 954 956 We we PRP 957 961 also also RB 962 970 examined examine VBD 971 974 the the DT 975 986 involvement involvement NN 987 989 of of IN 990 995 other other JJ 996 1002 signal signal NN 1003 1015 transduction transduction NN 1016 1024 pathways pathway NNS 1024 1025 . . . 1026 1034 Specific specific JJ 1035 1045 inhibitors inhibitor NNS 1046 1048 of of IN 1049 1063 p70(S6)-kinase p70(S6)-kinase NNP 1064 1065 ( ( ( 1065 1074 rapamycin rapamycin NN 1074 1075 ) ) ) 1075 1076 , , , 1077 1080 and and CC 1081 1083 Gi Gi NNP 1084 1091 protein protein NN 1092 1093 ( ( ( 1093 1102 pertussis pertussis NN 1103 1108 toxin toxin NN 1108 1109 ) ) ) 1109 1110 , , , 1111 1120 prevented prevent VBD 1121 1130 induction induction NN 1131 1133 of of IN 1134 1139 IL-10 il-10 NN 1140 1150 production production NN 1151 1153 by by IN 1154 1158 gp41 gp41 NN 1159 1161 in in IN 1162 1171 monocytes monocyte NNS 1171 1172 , , , 1173 1178 while while IN 1179 1189 inhibitors inhibitor NNS 1190 1192 of of IN 1193 1196 the the DT 1197 1217 phosphatidylinositol phosphatidylinositol NN 1218 1226 3-kinase 3-kinase NNP 1227 1228 ( ( ( 1228 1230 PI PI NNP 1231 1239 3-kinase 3-kinase NNP 1239 1240 ) ) ) 1241 1242 ( ( ( 1242 1252 wortmannin wortmannin NN 1252 1253 ) ) ) 1254 1257 and and CC 1258 1275 mitogen-activated mitogen-activated JJ 1276 1283 protein protein NN 1284 1290 kinase kinase NNP 1291 1292 ( ( ( 1292 1296 MAPK MAPK NNP 1296 1297 ) ) ) 1298 1305 pathway pathway NN 1306 1307 ( ( ( 1307 1309 PD PD NNP 1310 1315 98059 98059 CD 1315 1316 ) ) ) 1317 1320 did do VBD 1321 1324 not not RB 1324 1325 . . . 1326 1330 Thus thus RB 1331 1336 HIV-1 HIV-1 NNP 1337 1349 gp41-induced gp41-induced JJ 1350 1355 IL-10 il-10 NN 1356 1369 up-regulation up-regulation NN 1370 1372 in in IN 1373 1382 monocytes monocyte NNS 1383 1386 may may MD 1387 1390 not not RB 1391 1398 involve involve VB 1399 1408 NF-kappaB NF-kappaB NNP 1408 1409 , , , 1410 1414 MAPK MAPK NNP 1414 1415 , , , 1416 1418 or or CC 1419 1421 PI PI NNP 1422 1430 3-kinase 3-kinase NNP 1431 1441 activation activation NN 1441 1442 , , , 1443 1446 but but CC 1447 1453 rather rather RB 1454 1457 may may MD 1458 1465 operate operate VB 1466 1473 through through IN 1474 1484 activation activation NN 1485 1487 of of IN 1488 1497 adenylate adenylate NN 1498 1505 cyclase cyclase NN 1506 1509 and and CC 1510 1535 pertussis-toxin-sensitive pertussis-toxin-sensitive JJ 1536 1541 Gi/Go Gi/Go NNP 1542 1549 protein protein NN 1550 1552 to to TO 1553 1559 effect effect VB 1560 1574 p70(S6)-kinase p70(S6)-kinase NNP 1575 1585 activation activation NN 1585 1586 . . .