0 8 Estrogen Estrogen NNP 9 12 and and CC 13 25 progesterone progesterone NN 26 35 induction induction NN 36 38 of of IN 39 47 survival survival NN 48 50 of of IN 51 63 monoblastoid monoblastoid JJ 64 69 cells cell NNS 70 80 undergoing undergo VBG 81 98 TNF-alpha-induced tnf-alpha-induced JJ 99 108 apoptosis apoptosis NN 108 109 . . . 111 120 Induction Induction NNP 121 123 of of IN 124 133 apoptosis apoptosis NN 134 136 of of IN 137 150 mononucleated mononucleated JJ 151 156 cells cell NNS 157 159 is be VBZ 160 161 a a DT 162 175 physiological physiological JJ 176 183 process process NN 184 187 for for IN 188 198 regulating regulate VBG 199 202 the the DT 203 212 intensity intensity NN 213 215 of of IN 216 219 the the DT 220 226 immune immune JJ 227 235 response response NN 235 236 . . . 237 240 The the DT 241 247 female female JJ 248 255 steroid steroid NN 256 264 hormones hormone NNS 265 273 estrogen estrogen NN 274 275 ( ( ( 275 277 E2 e2 NN 277 278 ) ) ) 279 282 and and CC 283 295 progesterone progesterone NN 296 297 ( ( ( 297 301 Prog Prog NNP 301 302 ) ) ) 303 306 are be VBP 307 312 known know VBN 313 315 to to TO 316 324 modulate modulate VB 325 328 the the DT 329 339 reactivity reactivity NN 340 342 of of IN 343 346 the the DT 347 353 immune immune JJ 354 360 system system NN 360 361 ; ; : 362 370 recently recently RB 371 373 it it PRP 374 377 has have VBZ 378 382 been be VBN 383 395 demonstrated demonstrate VBN 396 400 that that IN 401 405 they they PRP 406 409 can can MD 410 418 regulate regulate VB 419 428 induction induction NN 429 431 of of IN 432 441 apoptosis apoptosis NN 442 444 of of IN 445 456 endothelial endothelial JJ 457 462 cells cell NNS 463 466 and and CC 467 478 osteoblasts osteoblast NNS 478 479 . . . 480 498 TNF-alpha-mediated tnf-alpha-mediated JJ 499 508 induction induction NN 509 511 of of IN 512 521 apoptosis apoptosis NN 522 525 has have VBZ 526 530 been be VBN 531 535 well well RB 536 549 characterized characterize VBN 550 552 in in IN 553 560 myeloid myeloid JJ 561 566 cells cell NNS 566 567 . . . 568 570 We we PRP 571 583 investigated investigate VBD 584 591 whether whether IN 592 594 E2 E2 NNP 595 598 and and CC 599 603 Prog Prog NNP 604 609 could could MD 610 619 interfere interfere VB 620 624 with with IN 625 642 TNF-alpha-induced tnf-alpha-induced JJ 643 652 apoptosis apoptosis NN 653 655 of of IN 656 659 the the DT 660 672 monoblastoid monoblastoid JJ 673 677 U937 u937 NN 678 682 cell cell NN 683 687 line line NN 687 688 . . . 689 698 Treatment Treatment NNP 699 703 with with IN 704 706 E2 E2 NNP 707 709 or or CC 710 714 Prog Prog NNP 715 724 increased increase VBD 725 733 survival survival NN 734 737 and and CC 738 747 prevented prevent VBD 748 757 apoptosis apoptosis NN 758 765 induced induce VBN 766 768 by by IN 769 778 TNF-alpha TNF-alpha NNP 779 781 in in IN 782 786 both both CC 787 803 undifferentiated undifferentiated JJ 804 807 and and CC 808 823 macrophage-like macrophage-like JJ 824 842 PMA-differentiated pma-differentiated JJ 843 847 U937 u937 NN 848 853 cells cell NNS 853 854 , , , 855 857 as as IN 858 866 assessed assess VBN 867 869 by by IN 870 876 trypan trypan NN 877 881 blue blue JJ 882 891 exclusion exclusion NN 892 896 cell cell NN 897 905 counting counting NN 905 906 , , , 907 916 thymidine thymidine NN 917 930 incorporation incorporation NN 930 931 , , , 932 940 AnnexinV AnnexinV NNP 941 949 labeling labeling NN 949 950 , , , 951 959 followed follow VBN 960 962 by by IN 963 967 flow flow NN 968 977 cytometry cytometry NN 978 981 and and CC 982 985 DNA dna NN 986 999 fragmentation fragmentation NN 1000 1007 studies study NNS 1007 1008 . . . 1009 1013 This this DT 1014 1020 effect effect NN 1021 1024 can can MD 1025 1027 be be VB 1028 1038 associated associate VBN 1039 1043 with with IN 1044 1047 the the DT 1048 1058 activation activation NN 1059 1061 of of IN 1062 1070 specific specific JJ 1071 1078 hormone hormone NN 1079 1088 receptors receptor NNS 1088 1089 , , , 1090 1095 since since IN 1096 1098 we we PRP 1099 1107 observed observe VBD 1108 1111 the the DT 1112 1122 expression expression NN 1123 1125 of of IN 1126 1129 the the DT 1130 1138 estrogen estrogen NN 1139 1147 receptor receptor NN 1148 1153 alpha alpha NN 1154 1155 ( ( ( 1155 1163 ER-alpha ER-alpha NNP 1163 1164 ) ) ) 1164 1165 , , , 1166 1173 ER-beta ER-beta NNP 1173 1174 , , , 1175 1178 and and CC 1179 1191 progesterone progesterone NN 1192 1200 receptor receptor NN 1201 1202 ( ( ( 1202 1204 PR PR NNP 1204 1205 ) ) ) 1206 1211 mRNAs mrna NNS 1211 1212 ; ; : 1213 1216 the the DT 1217 1225 ER-alpha ER-alpha NNP 1226 1233 protein protein NN 1234 1244 expression expression NN 1245 1248 was be VBD 1249 1258 confirmed confirm VBN 1259 1261 by by IN 1262 1280 immunocytochemical immunocytochemical JJ 1281 1289 analysis analysis NN 1289 1290 . . . 1291 1293 In in IN 1294 1302 addition addition NN 1302 1303 , , , 1304 1320 hormone-mediated hormone-mediated JJ 1321 1329 survival survival NN 1330 1337 against against IN 1338 1347 apoptosis apoptosis NN 1348 1351 was be VBD 1352 1365 concentration concentration NN 1366 1375 dependent dependent JJ 1375 1376 , , , 1377 1385 reaching reach VBG 1386 1389 the the DT 1390 1402 half-maximal half-maximal JJ 1403 1409 effect effect NN 1410 1412 at at IN 1413 1415 10 10 CD 1416 1418 nM nm NN 1419 1422 and and CC 1423 1430 blocked block VBN 1431 1433 by by IN 1434 1437 the the DT 1438 1440 ER ER NNP 1441 1451 antagonist antagonist NN 1452 1455 ICI ICI NNP 1456 1463 182,780 182,780 CD 1464 1466 in in IN 1467 1483 undifferentiated undifferentiated JJ 1484 1489 cells cell NNS 1489 1490 , , , 1491 1498 further further RB 1499 1509 supporting support VBG 1510 1511 a a DT 1512 1529 receptor-mediated receptor-mediated JJ 1530 1539 mechanism mechanism NN 1540 1542 of of IN 1543 1547 cell cell NN 1548 1556 survival survival NN 1556 1557 . . . 1558 1563 Other other JJ 1564 1571 steroid steroid NN 1572 1580 receptor receptor NN 1581 1586 drugs drug NNS 1587 1591 such such JJ 1592 1594 as as IN 1595 1605 Raloxifene Raloxifene NNP 1605 1606 , , , 1607 1612 RU486 ru486 NN 1612 1613 , , , 1614 1616 or or CC 1617 1620 the the DT 1621 1624 ICI ICI NNP 1625 1632 182,780 182,780 CD 1633 1635 in in IN 1636 1654 PMA-differentiated pma-differentiated JJ 1655 1660 cells cell NNS 1661 1670 displayed display VBD 1671 1678 agonist agonist NN 1679 1687 activity activity NN 1688 1690 by by IN 1691 1701 preventing prevent VBG 1702 1719 TNF-alpha-induced tnf-alpha-induced JJ 1720 1729 apoptosis apoptosis NN 1730 1732 as as RB 1733 1744 efficiently efficiently RB 1745 1747 as as IN 1748 1751 the the DT 1752 1760 hormones hormone NNS 1761 1766 alone alone RB 1766 1767 , , , 1768 1777 providing provide VBG 1778 1785 further further JJ 1786 1794 evidence evidence NN 1795 1797 to to TO 1798 1801 the the DT 1802 1808 notion notion NN 1809 1813 that that IN 1814 1821 steroid steroid NN 1822 1830 receptor receptor NN 1831 1836 drugs drug NNS 1837 1840 may may MD 1841 1849 manifest manifest VB 1850 1857 agonist agonist NN 1858 1860 or or CC 1861 1871 antagonist antagonist NN 1872 1882 activities activity NNS 1883 1892 depending depend VBG 1893 1895 on on IN 1896 1899 the the DT 1900 1908 cellular cellular JJ 1909 1916 context context NN 1917 1919 in in IN 1920 1925 which which WDT 1926 1930 they they PRP 1931 1934 are be VBP 1935 1942 studied study VBN 1942 1943 . . . 1944 1953 Treatment Treatment NNP 1954 1958 with with IN 1959 1961 E2 E2 NNP 1962 1965 was be VBD 1966 1970 also also RB 1971 1981 associated associate VBN 1982 1986 with with IN 1987 1988 a a DT 1989 2003 time-dependent time-dependent JJ 2004 2012 decrease decrease NN 2013 2015 in in IN 2016 2019 the the DT 2020 2024 mRNA mrna NN 2025 2030 level level NN 2031 2033 of of IN 2034 2037 the the DT 2038 2050 proapoptotic proapoptotic JJ 2051 2056 Nip-2 nip-2 NN 2057 2064 protein protein NN 2064 2065 , , , 2066 2076 supporting support VBG 2077 2080 the the DT 2081 2091 hypothesis hypothesis NN 2092 2096 that that IN 2097 2104 hormone hormone NN 2105 2119 responsiveness responsiveness NN 2120 2122 of of IN 2123 2127 U937 u937 NN 2128 2133 cells cell NNS 2134 2136 is be VBZ 2137 2145 mediated mediate VBN 2146 2148 by by IN 2149 2155 target target NN 2156 2160 gene gene NN 2161 2174 transcription transcription NN 2174 2175 . . . 2176 2184 Together together RB 2184 2185 , , , 2186 2191 these these DT 2192 2199 results result NNS 2200 2211 demonstrate demonstrate VBP 2212 2216 that that IN 2217 2219 ER ER NNP 2220 2223 and and CC 2224 2226 PR PR NNP 2227 2230 can can MD 2231 2233 be be VB 2234 2243 activated activate VBN 2244 2246 by by IN 2247 2257 endogenous endogenous JJ 2258 2260 or or CC 2261 2270 exogenous exogenous JJ 2271 2278 ligands ligand NNS 2279 2281 to to TO 2282 2288 induce induce VB 2289 2290 a a DT 2291 2298 genetic genetic JJ 2299 2307 response response NN 2308 2312 that that WDT 2313 2320 impairs impair VBZ 2321 2338 TNF-alpha-induced tnf-alpha-induced JJ 2339 2348 apoptosis apoptosis NN 2349 2351 in in IN 2352 2356 U937 u937 NN 2357 2362 cells cell NNS 2362 2363 . . . 2364 2367 The the DT 2368 2372 data datum NNS 2373 2382 presented present VBN 2383 2387 here here RB 2388 2395 suggest suggest VBP 2396 2400 that that IN 2401 2404 the the DT 2405 2411 female female JJ 2412 2419 steroid steroid NN 2420 2429 receptors receptor NNS 2430 2434 play play VBP 2435 2436 a a DT 2437 2441 role role NN 2442 2444 in in IN 2445 2455 regulation regulation NN 2456 2458 of of IN 2459 2462 the the DT 2463 2469 immune immune JJ 2470 2478 response response NN 2479 2481 by by IN 2482 2492 preventing prevent VBG 2493 2502 apoptosis apoptosis NN 2503 2505 of of IN 2506 2518 monoblastoid monoblastoid JJ 2519 2524 cells cell NNS 2524 2525 ; ; : 2526 2530 this this DT 2531 2537 effect effect NN 2538 2543 might might MD 2544 2548 have have VB 2549 2558 important important JJ 2559 2571 consequences consequence NNS 2572 2574 in in IN 2575 2578 the the DT 2579 2587 clinical clinical JJ 2588 2591 use use NN 2592 2594 of of IN 2595 2602 steroid steroid NN 2603 2611 receptor receptor NN 2612 2618 drugs. drugs. NN 2619 2627 –Vegeto –Vegeto NNP 2627 2628 , , , 2629 2631 E. E. NNP 2631 2632 , , , 2633 2639 Pollio Pollio NNP 2639 2640 , , , 2641 2643 G. G. NNP 2643 2644 , , , 2645 2656 Pellicciari Pellicciari NNP 2656 2657 , , , 2658 2660 C. C. NNP 2660 2661 , , , 2662 2667 Maggi Maggi NNP 2667 2668 , , , 2669 2671 A. A. NNP 2672 2680 Estrogen Estrogen NNP 2681 2684 and and CC 2685 2697 progesterone progesterone NN 2698 2707 induction induction NN 2708 2710 of of IN 2711 2719 survival survival NN 2720 2722 of of IN 2723 2735 monoblastoid monoblastoid JJ 2736 2741 cells cell NNS 2742 2752 undergoing undergo VBG 2753 2769 TNF-alpha-inuced tnf-alpha-inuced JJ 2770 2779 apoptosis apoptosis NN 2779 2780 . . .