0 12 Differential differential JJ 13 20 effects effect NNS 21 23 of of IN 24 31 protein protein NN 32 38 kinase kinase NNP 39 40 C C NNP 41 51 inhibitors inhibitor NNS 52 54 on on IN 55 74 fibronectin-induced fibronectin-induced JJ 75 91 interleukin-beta interleukin-beta NN 92 96 gene gene NN 97 110 transcription transcription NN 110 111 , , , 112 119 protein protein NN 120 129 synthesis synthesis NN 130 133 and and CC 134 143 secretion secretion NN 144 146 in in IN 147 152 human human JJ 153 162 monocytic monocytic JJ 163 168 cells cell NNS 168 169 . . . 171 176 Human human JJ 177 186 monocytic monocytic JJ 187 192 cells cell NNS 193 200 express express VBP 201 218 interleukin-1beta interleukin-1beta NN 219 220 ( ( ( 220 228 IL-1beta IL-1beta NNP 228 229 ) ) ) 230 234 when when WRB 235 245 stimulated stimulate VBN 246 250 with with IN 251 254 the the DT 255 268 extracellular extracellular JJ 269 275 matrix matrix NN 276 288 glycoprotein glycoprotein NN 288 289 , , , 290 301 fibronectin fibronectin NN 302 303 ( ( ( 303 307 FN). FN). NNP 308 315 Protein Protein NNP 316 322 kinase kinase NNP 323 324 C C NNP 325 326 ( ( ( 326 329 PKC PKC NNP 329 330 ) ) ) 331 341 activation activation NN 342 344 is be VBZ 345 355 considered consider VBN 356 365 important important JJ 366 369 for for IN 370 374 this this DT 375 382 process process NN 382 383 ; ; : 384 391 however however RB 391 392 , , , 393 396 the the DT 397 406 metabolic metabolic JJ 407 412 steps step NNS 413 415 at at IN 416 421 which which WDT 422 425 PKC PKC NNP 426 430 acts act VBZ 431 435 upon upon IN 436 438 to to TO 439 446 mediate mediate VB 447 450 the the DT 451 461 FN-induced fn-induced JJ 462 470 IL-1beta IL-1beta NNP 471 479 response response NN 480 486 remain remain VBP 487 494 unclear unclear JJ 494 495 . . . 496 498 We we PRP 499 508 performed perform VBD 509 511 an an DT 512 520 analysis analysis NN 521 523 of of IN 524 527 the the DT 528 538 mechanisms mechanism NNS 539 541 by by IN 542 547 which which WDT 548 551 two two CD 552 555 PKC PKC NNP 556 566 inhibitors inhibitor NNS 566 567 , , , 568 578 Calphostin Calphostin NNP 579 580 C C NNP 581 584 and and CC 585 598 Staurosporine Staurosporine NNP 598 599 , , , 600 607 prevent prevent VBP 608 611 the the DT 612 622 FN-induced fn-induced JJ 623 631 IL-1beta IL-1beta NNP 632 640 response response NN 640 641 . . . 642 646 Both both DT 647 657 inhibitors inhibitor NNS 658 665 blocked block VBD 666 669 the the DT 670 679 secretion secretion NN 680 682 of of IN 683 691 IL-1beta IL-1beta NNP 692 699 protein protein NN 700 704 into into IN 705 708 the the DT 709 714 media medium NNS 715 717 of of IN 718 728 peripheral peripheral JJ 729 734 blood blood NN 735 746 mononuclear mononuclear JJ 747 752 cells cell NNS 753 760 exposed expose VBN 761 763 to to TO 764 766 FN FN NNP 766 767 . . . 768 787 Immunoprecipitation Immunoprecipitation NNP 788 796 analysis analysis NN 797 805 revealed reveal VBD 806 810 that that IN 811 816 under under IN 817 822 these these DT 823 836 circumstances circumstance NNS 836 837 , , , 838 848 Calphostin Calphostin NNP 849 850 C C NNP 851 860 inhibited inhibit VBD 861 864 the the DT 865 875 production production NN 876 878 of of IN 879 887 IL-1beta IL-1beta NNP 888 895 protein protein NN 895 896 , , , 897 904 whereas whereas IN 905 918 Staurosporine Staurosporine NNP 919 926 allowed allow VBD 927 934 protein protein NN 935 945 production production NN 945 946 , , , 947 950 but but CC 951 960 inhibited inhibit VBD 961 964 its its PRP$ 965 974 secretion secretion NN 974 975 . . . 976 978 To to TO 979 988 determine determine VB 989 992 the the DT 993 1003 mechanisms mechanism NNS 1004 1015 responsible responsible JJ 1016 1019 for for IN 1020 1025 these these DT 1026 1037 differences difference NNS 1037 1038 , , , 1039 1041 we we PRP 1042 1048 turned turn VBD 1049 1051 to to TO 1052 1057 human human JJ 1058 1062 U937 u937 NN 1063 1075 promonocytic promonocytic JJ 1076 1081 cells cell NNS 1081 1082 . . . 1083 1087 U937 u937 NN 1088 1093 cells cell NNS 1094 1105 transfected transfecte VBN 1106 1110 with with IN 1111 1114 the the DT 1115 1120 human human JJ 1121 1132 full-length full-length JJ 1133 1141 IL-1beta IL-1beta NNP 1142 1150 promoter promoter NN 1151 1160 connected connect VBN 1161 1163 to to TO 1164 1165 a a DT 1166 1176 luciferase luciferase NN 1177 1185 reporter reporter NN 1186 1190 gene gene NN 1191 1195 were be VBD 1196 1205 submitted submit VBN 1206 1208 to to TO 1209 1222 transcription transcription NN 1223 1229 assays assay NNS 1229 1230 , , , 1231 1239 Northern Northern NNP 1240 1248 blotting blotting NN 1248 1249 , , , 1250 1253 and and CC 1254 1257 DNA DNA NNP 1258 1273 electrophoresis electrophoresis NN 1274 1282 mobility mobility NN 1283 1286 gel gel NN 1287 1292 shift shift NN 1293 1299 assays assay NNS 1299 1300 . . . 1301 1306 These these DT 1307 1314 studies study NNS 1315 1323 revealed reveal VBD 1324 1328 that that IN 1329 1339 Calphostin Calphostin NNP 1340 1341 C C NNP 1342 1351 inhibited inhibit VBD 1352 1355 the the DT 1356 1363 nuclear nuclear JJ 1364 1377 translocation translocation NN 1378 1380 of of IN 1381 1384 the the DT 1385 1398 transcription transcription NN 1399 1405 factor factor NN 1406 1415 activator activator NN 1416 1425 protein-1 protein-1 NN 1426 1427 ( ( ( 1427 1431 AP-1 ap-1 NN 1431 1432 ) ) ) 1433 1438 which which WDT 1439 1441 is be VBZ 1442 1452 considered consider VBN 1453 1462 necessary necessary JJ 1463 1466 for for IN 1467 1469 FN fn NN 1470 1479 induction induction NN 1480 1482 of of IN 1483 1491 IL-1beta IL-1beta NNP 1492 1496 gene gene NN 1497 1510 transcription transcription NN 1510 1511 , , , 1512 1515 and and CC 1516 1525 prevented prevent VBD 1526 1529 the the DT 1530 1543 transcription transcription NN 1544 1546 of of IN 1547 1550 the the DT 1551 1559 IL-1beta IL-1beta NNP 1560 1564 gene gene NN 1564 1565 . . . 1566 1568 In in IN 1569 1577 contrast contrast NN 1577 1578 , , , 1579 1592 Staurosporine Staurosporine NNP 1593 1598 alone alone RB 1599 1606 induced induce VBD 1607 1611 AP-1 ap-1 NN 1612 1625 translocation translocation NN 1626 1629 and and CC 1630 1641 stimulation stimulation NN 1642 1644 of of IN 1645 1648 the the DT 1649 1653 gene gene NN 1653 1654 . . . 1655 1662 Overall overall RB 1662 1663 , , , 1664 1667 our our PRP$ 1668 1672 data datum NNS 1673 1681 indicate indicate VBP 1682 1686 that that IN 1687 1697 Calphostin Calphostin NNP 1698 1699 C C NNP 1700 1708 prevents prevent VBZ 1709 1712 the the DT 1713 1726 transcription transcription NN 1727 1729 of of IN 1730 1733 the the DT 1734 1742 IL-1beta IL-1beta NNP 1743 1747 gene gene NN 1748 1755 thereby thereby RB 1756 1766 inhibiting inhibit VBG 1767 1774 protein protein NN 1775 1784 synthesis synthesis NN 1784 1785 . . . 1786 1791 Based base VBN 1792 1794 on on IN 1795 1798 the the DT 1799 1803 high high JJ 1804 1815 specificity specificity NN 1816 1818 of of IN 1819 1823 this this DT 1824 1832 compound compound NN 1833 1836 for for IN 1837 1840 PKC PKC NNP 1840 1841 , , , 1842 1844 we we PRP 1845 1853 conclude conclude VBP 1854 1858 that that IN 1859 1862 PKC PKC NNP 1863 1865 is be VBZ 1866 1875 necessary necessary JJ 1876 1879 for for IN 1880 1890 FN-induced fn-induced JJ 1891 1899 IL-1beta IL-1beta NNP 1900 1907 protein protein NN 1908 1918 production production NN 1918 1919 . . . 1920 1922 In in IN 1923 1931 contrast contrast NN 1931 1932 , , , 1933 1946 Staurosporine Staurosporine NNP 1947 1956 prevented prevent VBD 1957 1966 secretion secretion NN 1967 1969 of of IN 1970 1978 IL-1beta IL-1beta NNP 1979 1981 by by IN 1982 1989 unknown unknown JJ 1990 2000 mechanisms mechanism NNS 2000 2001 . . .