0 9 Monocytic monocytic JJ 10 14 cell cell NN 15 28 type-specific type-specific JJ 29 44 transcriptional transcriptional JJ 45 54 induction induction NN 55 57 of of IN 58 69 collagenase collagenase NN 69 70 . . . 72 84 Interstitial interstitial JJ 85 96 collagenase collagenase NN 97 98 ( ( ( 98 103 MMP-1 mmp-1 NN 103 104 ) ) ) 104 105 , , , 106 107 a a DT 108 125 metalloproteinase metalloproteinase NN 126 134 produced produce VBN 135 137 by by IN 138 146 resident resident JJ 147 150 and and CC 151 163 inflammatory inflammatory JJ 164 169 cells cell NNS 170 176 during during IN 177 187 connective connective JJ 188 194 tissue tissue NN 195 203 turnover turnover NN 203 204 , , , 205 212 cleaves cleave VBZ 213 217 type type NN 218 219 I i CD 220 228 collagen collagen NN 229 236 fibrils fibril NNS 236 237 . . . 238 242 This this DT 243 252 catalytic catalytic JJ 253 258 event event NN 259 261 is be VBZ 262 266 rate rate NN 267 275 limiting limit VBG 276 278 in in IN 279 289 remodeling remodeling NN 290 292 of of IN 293 300 tissues tissue NNS 301 305 rich rich JJ 306 308 in in IN 309 318 fibrillar fibrillar JJ 319 327 collagen collagen NN 328 332 such such JJ 333 335 as as IN 336 339 the the DT 340 344 skin skin NN 345 348 and and CC 349 354 lungs lung NNS 354 355 . . . 356 359 The the DT 360 370 regulation regulation NN 371 373 of of IN 374 385 collagenase collagenase NN 386 396 expression expression NN 397 399 is be VBZ 400 409 cell-type cell-type JJ 410 418 specific specific JJ 418 419 ; ; : 420 429 bacterial bacterial JJ 430 433 LPS lps NN 434 437 and and CC 438 445 zymosan zymosan NN 445 446 , , , 447 448 a a DT 449 454 yeast yeast NN 455 459 cell cell NN 460 464 wall wall NN 465 475 derivative derivative NN 475 476 , , , 477 480 are be VBP 481 487 potent potent JJ 488 496 inducers inducer NNS 497 499 of of IN 500 511 collagenase collagenase NN 512 522 expression expression NN 523 525 in in IN 526 537 macrophages macrophage NNS 537 538 , , , 539 542 but but CC 543 545 do do VBP 546 549 not not RB 550 555 alter alter VB 556 566 fibroblast fibroblast NN 567 578 collagenase collagenase NN 579 589 expression expression NN 589 590 . . . 591 596 Since since IN 597 605 promoter promoter NN 606 614 elements element NNS 615 626 controlling control VBG 627 638 collagenase collagenase NN 639 652 transcription transcription NN 653 655 in in IN 656 665 monocytic monocytic JJ 666 671 cells cell NNS 672 676 have have VBP 677 680 not not RB 681 685 been be VBN 686 696 previously previously RB 697 704 defined define VBN 704 705 , , , 706 708 we we PRP 709 715 sought seek VBD 716 718 to to TO 719 728 delineate delineate VB 729 739 responsive responsive JJ 740 750 cis-acting cis-acting JJ 751 759 elements element NNS 760 762 of of IN 763 766 the the DT 767 778 collagenase collagenase NN 779 787 promoter promoter NN 788 790 in in IN 791 802 transiently transiently RB 803 814 transfected transfecte VBN 815 820 human human JJ 821 822 ( ( ( 822 826 U937 u937 NN 826 827 ) ) ) 828 831 and and CC 832 838 murine murine JJ 839 840 ( ( ( 840 844 J774 j774 NN 844 845 ) ) ) 846 855 monocytic monocytic JJ 856 860 cell cell NN 861 866 lines line NNS 866 867 . . . 868 876 Deletion deletion NN 877 887 constructs construct NNS 888 898 containing contain VBG 899 901 as as RB 902 908 little little JJ 909 911 as as IN 912 914 72 72 CD 915 917 bp bp NN 918 920 of of IN 921 922 5 5 CD 922 923 ’ ' SYM 924 933 -flanking -flanking JJ 934 942 sequence sequence NN 943 945 of of IN 946 949 the the DT 950 961 collagenase collagenase NN 962 970 promoter promoter NN 971 975 were be VBD 976 986 sufficient sufficient JJ 987 990 for for IN 991 995 LPS- lps- NN 996 998 or or CC 999 1015 zymosan-mediated zymosan-mediated JJ 1016 1031 transcriptional transcriptional JJ 1032 1041 induction induction NN 1041 1042 , , , 1043 1050 whereas whereas IN 1051 1058 phorbol phorbol NN 1059 1071 inducibility inducibility NN 1072 1081 exhibited exhibit VBD 1082 1084 an an DT 1085 1093 absolute absolute JJ 1094 1105 requirement requirement NN 1106 1109 for for IN 1110 1118 upstream upstream JJ 1119 1127 elements element NNS 1128 1137 including include VBG 1138 1141 the the DT 1142 1149 polyoma polyoma NN 1150 1158 enhancer enhancer NN 1159 1168 A-binding a-binding JJ 1169 1178 protein-3 protein-3 NN 1179 1183 site site NN 1184 1185 ( ( ( 1185 1188 -83 -83 CD 1189 1191 to to TO 1192 1195 -91 -91 CD 1195 1196 ) ) ) 1197 1200 and and CC 1201 1205 TTCA TTCA NNP 1206 1214 sequence sequence NN 1215 1216 ( ( ( 1216 1220 -102 -102 CD 1221 1223 to to TO 1224 1228 -105 -105 CD 1228 1229 ) ) ) 1230 1232 in in IN 1233 1237 both both CC 1238 1247 monocytic monocytic JJ 1248 1253 cells cell NNS 1254 1257 and and CC 1258 1269 fibroblasts fibroblast NNS 1269 1270 . . . 1271 1282 Mutagenesis Mutagenesis NNP 1283 1285 of of IN 1286 1289 the the DT 1290 1299 activator activator NN 1300 1309 protein-1 protein-1 NN 1310 1311 [ [ ( 1311 1315 AP-1 ap-1 NN 1315 1316 ] ] ) 1317 1321 site site NN 1322 1324 at at IN 1325 1328 -72 -72 CD 1329 1338 abolished abolish VBD 1339 1344 basal basal JJ 1345 1353 promoter promoter NN 1354 1362 activity activity NN 1363 1366 and and CC 1367 1378 LPS/zymosan lps/zymosan NN 1379 1391 inducibility inducibility NN 1391 1392 , , , 1393 1398 while while IN 1399 1410 mutagenesis mutagenesis NN 1411 1413 of of IN 1414 1416 an an DT 1417 1431 NF-kappaB-like nf-kappab-like JJ 1432 1436 site site NN 1437 1439 at at IN 1440 1443 -20 -20 CD 1444 1446 to to TO 1447 1450 -10 -10 CD 1451 1454 had have VBD 1455 1457 no no DT 1458 1464 effect effect NN 1464 1465 . . . 1466 1473 Nuclear nuclear JJ 1474 1482 extracts extract NNS 1483 1487 from from IN 1488 1492 LPS- lps- NN 1493 1496 and and CC 1497 1512 zymosan-treated zymosan-treated JJ 1513 1518 cells cell NNS 1519 1525 showed show VBD 1526 1532 strong strong JJ 1533 1537 AP-1 ap-1 NN 1538 1546 activity activity NN 1547 1549 by by IN 1550 1559 gel-shift gel-shift JJ 1560 1568 analysis analysis NN 1568 1569 , , , 1570 1573 and and CC 1574 1584 supershift supershift NN 1585 1593 analysis analysis NN 1594 1600 showed show VBD 1601 1604 the the DT 1605 1609 AP-1 ap-1 NN 1610 1619 complexes complex NNS 1620 1629 contained contain VBD 1630 1638 specific specific JJ 1639 1646 members member NNS 1647 1649 of of IN 1650 1654 both both CC 1655 1658 the the DT 1659 1662 jun jun NN 1663 1666 and and CC 1667 1670 fos fos NN 1671 1675 gene gene NN 1676 1684 families family NNS 1684 1685 . . . 1686 1691 These these DT 1692 1696 data datum NNS 1697 1705 indicate indicate VBP 1706 1710 that that IN 1710 1711 , , , 1712 1714 in in IN 1715 1723 contrast contrast NN 1724 1726 to to TO 1727 1731 most most JJS 1732 1735 LPS LPS NNP 1736 1743 effects effect NNS 1743 1744 , , , 1745 1749 AP-1 ap-1 NN 1749 1750 , , , 1751 1754 but but CC 1755 1758 not not RB 1759 1766 nuclear nuclear JJ 1767 1780 factor-kappaB factor-kappab NN 1780 1781 , , , 1782 1790 mediates mediate VBZ 1791 1794 LPS LPS NNP 1795 1804 induction induction NN 1805 1807 of of IN 1808 1819 collagenase collagenase NN 1820 1833 transcription transcription NN 1834 1836 in in IN 1837 1851 macrophagelike macrophagelike JJ 1852 1857 cells cell NNS 1857 1858 . . . 1859 1870 Furthermore furthermore RB 1870 1871 , , , 1872 1874 as as IN 1875 1883 compared compare VBN 1884 1886 to to TO 1887 1897 regulation regulation NN 1898 1900 by by IN 1901 1908 phorbol phorbol NN 1909 1914 ester ester NN 1914 1915 , , , 1916 1927 collagenase collagenase NN 1928 1937 induction induction NN 1938 1940 in in IN 1941 1950 monocytic monocytic JJ 1951 1956 cells cell NNS 1957 1959 by by IN 1960 1964 cell cell NN 1965 1969 wall wall NN 1970 1981 derivatives derivative NNS 1982 1984 of of IN 1985 1993 bacteria bacteria NNS 1994 1996 or or CC 1997 2002 yeast yeast NN 2003 2005 is be VBZ 2006 2013 largely largely RB 2014 2025 independent independent JJ 2026 2028 of of IN 2029 2037 upstream upstream JJ 2038 2046 promoter promoter NN 2047 2056 sequences sequence NNS 2056 2057 . . .