0 10 Regulation regulation NN 11 13 of of IN 14 17 jun jun NN 18 21 and and CC 22 25 fos fos NN 26 30 gene gene NN 31 41 expression expression NN 42 44 in in IN 45 50 human human JJ 51 60 monocytes monocyte NNS 61 63 by by IN 64 67 the the DT 68 78 macrophage macrophage NN 79 97 colony-stimulating colony-stimulating JJ 98 104 factor factor NN 104 105 . . . 107 110 The the DT 111 121 macrophage macrophage NN 122 140 colony-stimulating colony-stimulating JJ 141 147 factor factor NN 148 149 ( ( ( 149 154 M-CSF M-CSF NNP 154 155 ) ) ) 156 158 is be VBZ 159 167 required require VBN 168 171 for for IN 172 175 the the DT 176 182 growth growth NN 183 186 and and CC 187 202 differentiation differentiation NN 203 205 of of IN 206 217 mononuclear mononuclear JJ 218 228 phagocytes phagocyte NNS 228 229 . . . 230 237 However however RB 237 238 , , , 239 242 the the DT 243 252 signaling signaling NN 253 259 events event NNS 260 271 responsible responsible JJ 272 275 for for IN 276 281 these these DT 282 289 effects effect NNS 290 296 remain remain VBP 297 304 unclear unclear JJ 304 305 . . . 306 309 The the DT 310 317 present present JJ 318 325 studies study NNS 326 330 have have VBP 331 339 examined examine VBN 340 343 the the DT 344 351 effects effect NNS 352 354 of of IN 355 360 M-CSF M-CSF NNP 361 363 on on IN 364 373 potential potential JJ 374 383 signaling signaling NN 384 392 pathways pathway NNS 393 402 involving involve VBG 403 413 expression expression NN 414 416 of of IN 417 420 the the DT 421 424 jun jun NN 425 428 and and CC 429 432 fos fos NN 433 438 early early JJ 439 447 response response NN 448 453 genes gene NNS 453 454 . . . 455 458 Low low JJ 459 465 levels level NNS 466 468 of of IN 469 474 c-jun c-jun NN 475 486 transcripts transcript NNS 487 491 were be VBD 492 502 detectable detectable JJ 503 505 in in IN 506 513 resting rest VBG 514 519 human human JJ 520 530 peripheral peripheral JJ 531 536 blood blood NN 537 546 monocytes monocyte NNS 546 547 . . . 548 557 Treatment Treatment NNP 558 560 of of IN 561 566 these these DT 567 572 cells cell NNS 573 577 with with IN 578 583 10(3) 10(3) CD 584 592 units/ml units/ml NN 593 598 human human JJ 599 610 recombinant recombinant JJ 611 616 M-CSF M-CSF NNP 617 620 was be VBD 621 631 associated associate VBN 632 636 with with IN 637 642 rapid rapid JJ 643 646 and and CC 647 656 transient transient JJ 657 666 increases increase NNS 667 669 in in IN 670 675 c-jun c-jun NN 676 680 mRNA mrna NN 681 687 levels level NNS 687 688 . . . 689 696 Nuclear nuclear JJ 697 703 run-on run-on JJ 704 710 assays assay NNS 711 714 and and CC 715 719 mRNA mrna NN 720 729 stability stability NN 730 737 studies study NNS 738 750 demonstrated demonstrate VBD 751 755 that that IN 756 761 M-CSF M-CSF NNP 762 771 regulates regulate VBZ 772 777 c-jun c-jun NN 778 788 expression expression NN 789 791 by by IN 792 796 both both CC 797 799 an an DT 800 808 increase increase NN 809 811 in in IN 812 825 transcription transcription NN 826 830 rate rate NN 831 834 and and CC 835 836 a a DT 837 849 prolongation prolongation NN 850 852 in in IN 853 856 the the DT 857 866 half-life half-life NN 867 869 of of IN 870 875 c-jun c-jun NN 876 887 transcripts transcript NNS 887 888 . . . 889 894 M-CSF M-CSF NNP 895 904 treatment treatment NN 905 908 was be VBD 909 913 also also RB 914 924 associated associate VBN 925 929 with with IN 930 931 a a DT 932 937 rapid rapid JJ 938 947 induction induction NN 948 950 of of IN 951 954 the the DT 955 960 jun-B jun-b NN 961 965 gene gene NN 965 966 , , , 967 975 although although IN 976 986 expression expression NN 987 989 of of IN 990 994 this this DT 995 999 gene gene NN 1000 1003 was be VBD 1004 1013 prolonged prolong VBN 1014 1022 compared compare VBN 1023 1025 to to TO 1026 1030 that that DT 1031 1033 of of IN 1034 1039 c-jun c-jun NN 1039 1040 . . . 1041 1043 We we PRP 1044 1051 further further RB 1052 1063 demonstrate demonstrate VBP 1064 1068 that that IN 1069 1074 M-CSF M-CSF NNP 1075 1084 increases increase VBZ 1085 1090 c-fos c-fos NN 1091 1095 mRNA mrna NN 1096 1102 levels level NNS 1103 1105 in in IN 1106 1111 human human JJ 1112 1121 monocytes monocyte NNS 1122 1129 through through IN 1130 1137 control control NN 1138 1140 at at IN 1141 1145 both both CC 1146 1149 the the DT 1150 1165 transcriptional transcriptional JJ 1166 1169 and and CC 1170 1189 posttranscriptional posttranscriptional JJ 1190 1196 levels level NNS 1196 1197 . . . 1198 1205 Maximal maximal JJ 1206 1215 induction induction NN 1216 1218 of of IN 1219 1222 the the DT 1223 1228 c-fos c-fos NN 1229 1233 gene gene NN 1234 1237 was be VBD 1238 1246 followed follow VBN 1247 1249 by by IN 1250 1254 that that DT 1255 1258 for for IN 1259 1262 the the DT 1263 1268 fos-B fos-b NN 1269 1273 gene gene NN 1273 1274 . . . 1275 1283 Moreover moreover RB 1283 1284 , , , 1285 1298 M-CSF-induced m-csf-induced JJ 1299 1309 expression expression NN 1310 1312 of of IN 1313 1316 the the DT 1317 1328 fos-related fos-related JJ 1329 1333 gene gene NN 1333 1334 , , , 1335 1340 fra-1 fra-1 NN 1340 1341 , , , 1342 1345 was be VBD 1346 1353 delayed delay VBN 1354 1362 compared compare VBN 1363 1365 to to TO 1366 1370 that that DT 1371 1374 for for IN 1375 1379 both both CC 1380 1385 c-fos c-fos NN 1386 1389 and and CC 1390 1395 fos-B fos-b NN 1395 1396 . . . 1397 1402 Taken take VBN 1403 1411 together together RB 1411 1412 , , , 1413 1416 the the DT 1417 1424 results result NNS 1425 1433 indicate indicate VBP 1434 1438 that that IN 1439 1444 M-CSF M-CSF NNP 1445 1454 treatment treatment NN 1455 1457 is be VBZ 1458 1468 associated associate VBN 1469 1473 with with IN 1474 1486 differential differential JJ 1487 1497 activation activation NN 1498 1500 of of IN 1501 1509 multiple multiple JJ 1510 1517 members member NNS 1518 1520 of of IN 1521 1524 the the DT 1525 1532 jun/fos jun/fos NN 1533 1539 family family NN 1540 1543 and and CC 1544 1548 that that IN 1549 1559 expression expression NN 1560 1562 of of IN 1563 1568 these these DT 1569 1574 genes gene NNS 1575 1580 could could MD 1581 1591 contribute contribute VB 1592 1594 to to TO 1595 1602 nuclear nuclear JJ 1603 1612 signaling signaling NN 1613 1623 mechanisms mechanism NNS 1624 1628 that that WDT 1629 1637 regulate regulate VBP 1638 1639 a a DT 1640 1648 specific specific JJ 1649 1656 program program NN 1657 1659 of of IN 1660 1668 monocyte monocyte NN 1669 1684 differentiation differentiation NN 1684 1685 . . .