0 15 Transcriptional transcriptional JJ 16 26 regulation regulation NN 27 29 of of IN 30 39 lysosomal lysosomal JJ 40 44 acid acid NN 45 51 lipase lipase NN 52 54 in in IN 55 70 differentiating differentiate VBG 71 80 monocytes monocyte NNS 81 83 is be VBZ 84 92 mediated mediate VBN 93 95 by by IN 96 109 transcription transcription NN 110 117 factors factor NNS 118 121 Sp1 sp1 NN 122 125 and and CC 126 130 AP-2 ap-2 NN 130 131 . . . 133 138 Human human JJ 139 148 lysosomal lysosomal JJ 149 153 acid acid NN 154 160 lipase lipase NN 161 162 ( ( ( 162 165 LAL LAL NNP 165 166 ) ) ) 167 169 is be VBZ 170 171 a a DT 172 181 hydrolase hydrolase NN 182 190 required require VBN 191 194 for for IN 195 198 the the DT 199 207 cleavage cleavage NN 208 210 of of IN 211 222 cholesteryl cholesteryl NN 223 229 esters ester NNS 230 233 and and CC 234 247 triglycerides triglyceride NNS 248 255 derived derive VBN 256 260 from from IN 261 267 plasma plasma NN 268 280 lipoproteins lipoprotein NNS 280 281 . . . 282 284 It it PRP 285 287 is be VBZ 288 293 shown show VBN 294 298 here here RB 299 303 that that IN 304 310 during during IN 311 319 monocyte monocyte NN 320 322 to to TO 323 333 macrophage macrophage NN 334 349 differentiation differentiation NN 349 350 , , , 351 354 the the DT 355 365 expression expression NN 366 368 of of IN 369 377 LAL-mRNA LAL-mRNA NNP 378 380 is be VBZ 381 388 induced induce VBN 388 389 . . . 390 394 This this DT 395 404 induction induction NN 405 407 is be VBZ 408 417 dependent dependent JJ 418 420 on on IN 421 428 protein protein NN 429 435 kinase kinase NNP 436 437 C C NNP 438 446 activity activity NN 447 450 and and CC 451 458 protein protein NN 459 468 synthesis synthesis NN 468 469 . . . 470 473 The the DT 474 478 cell cell NN 479 492 type-specific type-specific JJ 493 501 increase increase NN 502 504 in in IN 505 508 LAL lal NN 509 519 expression expression NN 520 522 is be VBZ 523 530 further further RBR 531 543 investigated investigate VBN 544 546 in in IN 547 550 the the DT 551 556 THP-1 thp-1 NN 557 561 cell cell NN 562 566 line line NN 567 571 with with IN 572 579 respect respect NN 580 582 to to TO 583 598 transcriptional transcriptional JJ 599 609 regulation regulation NN 609 610 . . . 611 614 The the DT 615 620 human human JJ 621 630 monocytic monocytic JJ 631 639 leukemia leukemia NN 640 644 cell cell NN 645 649 line line NN 650 655 THP-1 thp-1 NN 656 670 differentiates differentiate VBZ 671 675 into into IN 676 691 macrophage-like macrophage-like JJ 692 697 cells cell NNS 698 702 when when WRB 703 710 treated treat VBN 711 715 with with IN 716 723 phorbol phorbol NN 724 730 esters ester NNS 730 731 . . . 732 734 In in IN 735 740 order order NN 741 743 to to TO 744 753 determine determine VB 754 757 the the DT 758 768 cis-acting cis-acting JJ 769 777 elements element NNS 778 787 necessary necessary JJ 788 791 for for IN 792 796 both both CC 797 802 basal basal JJ 803 806 and and CC 807 814 phorbol phorbol NN 815 830 12-myristate-13 12-myristate-13 NN 831 838 acetate acetate NN 839 840 ( ( ( 840 853 PMA)-enhanced pma)-enhanced JJ 854 862 promoter promoter NN 863 871 activity activity NN 871 872 , , , 873 875 we we PRP 876 885 performed perform VBD 886 894 deletion deletion NN 895 903 analysis analysis NN 904 907 and and CC 908 916 reporter reporter NN 917 921 gene gene NN 922 928 assays assay NNS 928 929 . . . 930 931 A a DT 932 935 PMA PMA NNP 936 946 responsive responsive JJ 947 954 element element NN 955 958 has have VBZ 959 963 been be VBN 964 974 identified identify VBN 975 982 between between IN 983 987 -182 -182 CD 988 990 bp bp NN 991 994 and and CC 995 999 -107 -107 CD 1000 1002 bp bp NN 1003 1011 upstream upstream RB 1012 1014 of of IN 1015 1018 the the DT 1019 1024 major major JJ 1025 1038 transcription transcription NN 1039 1044 start start NN 1045 1049 site site NN 1049 1050 . . . 1051 1054 Gel Gel NNP 1055 1063 mobility mobility NN 1064 1069 shift shift NN 1070 1076 assays assay NNS 1077 1089 demonstrated demonstrate VBD 1090 1094 that that IN 1095 1102 binding binding NN 1103 1105 of of IN 1106 1109 Sp1 sp1 NN 1110 1113 and and CC 1114 1118 AP-2 ap-2 NN 1119 1121 to to TO 1122 1125 the the DT 1126 1129 LAL lal NN 1130 1138 promoter promoter NN 1139 1141 is be VBZ 1142 1151 increased increase VBN 1152 1154 by by IN 1155 1158 PMA PMA NNP 1159 1161 in in IN 1162 1167 THP-1 thp-1 NN 1168 1173 cells cell NNS 1173 1174 . . . 1175 1191 Co-transfections co-transfection NNS 1192 1196 with with IN 1197 1207 expression expression NN 1208 1216 plasmids plasmid NNS 1217 1220 for for IN 1221 1224 Sp1 Sp1 NNP 1225 1228 and and CC 1229 1233 AP-2 AP-2 NNP 1234 1241 further further RBR 1242 1252 emphasized emphasize VBD 1253 1256 the the DT 1257 1266 important important JJ 1267 1271 role role NN 1272 1274 of of IN 1275 1280 these these DT 1281 1294 transcription transcription NN 1295 1302 factors factor NNS 1303 1305 in in IN 1306 1310 both both CC 1311 1316 basal basal JJ 1317 1320 and and CC 1321 1333 PMA-enhanced pma-enhanced JJ 1334 1337 LAL lal NN 1338 1348 expression expression NN 1348 1349 . . . 1350 1353 Our our PRP$ 1354 1358 data datum NNS 1359 1366 suggest suggest VBP 1367 1371 that that IN 1372 1387 differentiation differentiation NN 1388 1397 dependent dependent JJ 1398 1406 increase increase NN 1407 1409 of of IN 1410 1419 lysosomal lysosomal JJ 1420 1424 acid acid NN 1425 1431 lipase lipase NN 1432 1433 ( ( ( 1433 1436 LAL LAL NNP 1436 1437 ) ) ) 1438 1448 expression expression NN 1449 1451 in in IN 1452 1457 THP-1 thp-1 NN 1458 1463 cells cell NNS 1464 1466 is be VBZ 1467 1475 mediated mediate VBN 1476 1478 by by IN 1479 1480 a a DT 1481 1490 concerted concerted JJ 1491 1497 action action NN 1498 1500 of of IN 1501 1504 Sp1 Sp1 NNP 1505 1508 and and CC 1509 1513 AP-2 ap-2 NN 1513 1514 . . .