0 11 Suppressive suppressive JJ 12 19 effects effect NNS 20 22 of of IN 23 40 anti-inflammatory anti-inflammatory JJ 41 47 agents agent NNS 48 50 on on IN 51 56 human human JJ 57 68 endothelial endothelial JJ 69 73 cell cell NN 74 84 activation activation NN 85 88 and and CC 89 98 induction induction NN 99 101 of of IN 102 106 heat heat NN 107 112 shock shock NN 113 121 proteins protein NNS 121 122 . . . 124 134 BACKGROUND background NN 134 135 : : : 136 143 Studies study NNS 144 148 from from IN 149 152 our our PRP$ 153 163 laboratory laboratory NN 164 168 have have VBP 169 174 shown show VBN 175 179 that that IN 180 183 the the DT 184 192 earliest early JJS 193 199 stages stage NNS 200 202 of of IN 203 218 atherosclerosis atherosclerosis NN 219 222 may may MD 223 225 be be VB 226 234 mediated mediate VBN 235 237 by by IN 238 240 an an DT 241 251 autoimmune autoimmune JJ 252 260 reaction reaction NN 261 268 against against IN 269 273 heat heat NN 274 279 shock shock NN 280 287 protein protein NN 288 290 60 60 CD 291 292 ( ( ( 292 297 Hsp60 hsp60 NN 297 298 ) ) ) 298 299 . . . 300 303 The the DT 304 316 interactions interaction NNS 317 319 of of IN 320 334 Hsp60-specific hsp60-specific JJ 335 336 T t NN 337 342 cells cell NNS 343 347 with with IN 348 356 arterial arterial JJ 357 368 endothelial endothelial JJ 369 374 cells cell NNS 375 376 ( ( ( 376 378 EC EC NNP 378 379 ) ) ) 380 387 require require VBP 388 398 expression expression NN 399 401 of of IN 402 406 both both CC 407 412 Hsp60 hsp60 NN 413 416 and and CC 417 424 certain certain JJ 425 433 adhesion adhesion NN 434 443 molecules molecule NNS 444 449 shown show VBN 450 452 to to TO 453 455 be be VB 456 463 induced induce VBN 464 478 simultaneously simultaneously RB 479 481 in in IN 482 484 EC EC NNP 485 487 by by IN 488 498 mechanical mechanical JJ 499 502 and and CC 503 508 other other JJ 509 514 types type NNS 515 517 of of IN 518 524 stress stress NN 524 525 . . . 526 534 Recently recently RB 534 535 , , , 536 538 it it PRP 539 542 was be VBD 543 548 shown show VBN 549 553 that that IN 554 565 suppression suppression NN 566 568 of of IN 569 570 T t NN 571 584 cell-mediated cell-mediated JJ 585 591 immune immune JJ 592 601 responses response NNS 602 604 by by IN 605 616 cyclosporin cyclosporin NN 617 618 A A NNP 619 620 ( ( ( 620 623 CyA CyA NNP 623 624 ) ) ) 625 633 enhanced enhance VBD 634 649 atherosclerotic atherosclerotic JJ 650 656 lesion lesion NN 657 666 formation formation NN 667 669 in in IN 670 674 mice mouse NNS 674 675 . . . 676 678 In in IN 679 687 contrast contrast NN 687 688 , , , 689 696 aspirin aspirin NN 697 700 was be VBD 701 706 found find VBN 707 709 to to TO 710 715 lower lower VB 716 719 the the DT 720 724 risk risk NN 725 727 of of IN 728 738 myocardial myocardial JJ 739 749 infarction infarction NN 750 752 in in IN 753 756 men man NNS 756 757 . . . 758 763 These these DT 764 775 conflicting conflict VBG 776 788 observations observation NNS 789 792 may may MD 793 795 be be VB 796 799 due due JJ 800 802 to to TO 803 812 different different JJ 813 820 effects effect NNS 821 823 of of IN 824 841 anti-inflammatory anti-inflammatory JJ 842 848 agents agent NNS 849 851 on on IN 852 860 adhesion adhesion NN 861 869 molecule molecule NN 870 873 and and CC 874 877 Hsp hsp NN 878 888 expression expression NN 889 891 in in IN 892 894 EC EC NNP 894 895 , , , 896 908 respectively respectively RB 908 909 . . . 910 918 MATERIAL material NN 919 922 AND and CC 923 930 METHODS methods NNS 930 931 : : : 932 934 In in IN 935 938 the the DT 939 946 present present JJ 947 952 study study NN 952 953 , , , 954 956 we we PRP 957 965 analyzed analyze VBD 966 969 the the DT 970 977 effects effect NNS 978 980 of of IN 981 984 CyA CyA NNP 984 985 , , , 986 993 aspirin aspirin NN 993 994 , , , 995 998 and and CC 999 1011 indomethacin indomethacin NN 1012 1014 on on IN 1015 1016 T t NN 1017 1021 cell cell NN 1022 1035 proliferation proliferation NN 1036 1041 using use VBG 1042 1043 a a DT 1044 1057 proliferation proliferation NN 1058 1063 assay assay NN 1063 1064 . . . 1065 1067 To to TO 1068 1075 explore explore VB 1076 1079 the the DT 1080 1090 expression expression NN 1091 1093 of of IN 1094 1102 adhesion adhesion NN 1103 1112 molecules molecule NNS 1112 1113 , , , 1114 1122 monocyte monocyte NN 1123 1138 chemoattractant chemoattractant NN 1139 1148 protein-1 protein-1 NN 1149 1150 ( ( ( 1150 1155 MCP-1 mcp-1 NN 1155 1156 ) ) ) 1156 1157 , , , 1158 1161 and and CC 1162 1167 Hsp60 hsp60 NN 1168 1170 in in IN 1171 1176 human human JJ 1177 1186 umbilical umbilical JJ 1187 1191 vein vein NN 1192 1203 endothelial endothelial JJ 1204 1209 cells cell NNS 1210 1211 ( ( ( 1211 1217 HUVECs HUVEC NNP 1217 1218 ) ) ) 1218 1219 , , , 1220 1228 Northern Northern NNP 1229 1233 blot blot NN 1234 1242 analyses analysis NNS 1243 1247 were be VBD 1248 1252 used use VBN 1252 1253 . . . 1254 1256 To to TO 1257 1264 examine examine VB 1265 1268 the the DT 1269 1279 activation activation NN 1280 1286 status status NN 1287 1289 of of IN 1290 1293 the the DT 1294 1307 transcription transcription NN 1308 1315 factors factor NNS 1316 1323 nuclear nuclear JJ 1324 1330 factor factor NN 1331 1337 kappaB kappaB NNP 1338 1339 ( ( ( 1339 1348 NF-kappaB NF-kappaB NNP 1348 1349 ) ) ) 1350 1353 and and CC 1354 1358 heat heat NN 1359 1364 shock shock NN 1365 1373 factor-1 factor-1 NN 1374 1375 ( ( ( 1375 1380 HSF-1 hsf-1 NN 1380 1381 ) ) ) 1381 1382 , , , 1383 1398 electrophoretic electrophoretic JJ 1399 1407 mobility mobility NN 1408 1413 shift shift NN 1414 1420 assays assay NNS 1421 1425 were be VBD 1426 1435 performed perform VBN 1435 1436 . . . 1437 1444 RESULTS results NNS 1444 1445 : : : 1446 1450 With with IN 1451 1454 the the DT 1455 1464 exception exception NN 1465 1467 of of IN 1468 1480 indomethacin indomethacin NN 1480 1481 , , , 1482 1485 the the DT 1486 1490 used use VBN 1491 1508 immunosuppressive immunosuppressive JJ 1509 1512 and and CC 1513 1530 anti-inflammatory anti-inflammatory JJ 1531 1537 agents agent NNS 1538 1551 significantly significantly RB 1552 1561 inhibited inhibit VBD 1562 1563 T t NN 1564 1568 cell cell NN 1569 1582 proliferation proliferation NN 1583 1585 in in IN 1586 1594 response response NN 1595 1597 to to TO 1598 1607 influenza influenza NN 1608 1613 virus virus NN 1614 1621 antigen antigen NN 1622 1624 in in IN 1625 1626 a a DT 1627 1641 dose-dependent dose-dependent JJ 1642 1648 manner manner NN 1648 1649 . . . 1650 1663 Interestingly interestingly RB 1663 1664 , , , 1665 1668 CyA CyA NNP 1669 1672 and and CC 1673 1685 indomethacin indomethacin NN 1686 1689 did do VBD 1690 1693 not not RB 1694 1702 suppress suppress VB 1703 1708 tumor tumor NN 1709 1717 necrosis necrosis NN 1718 1730 factor-alpha factor-alpha NN 1731 1732 ( ( ( 1732 1750 TNF-alpha)-induced tnf-alpha)-induced JJ 1751 1759 adhesion adhesion NN 1760 1768 molecule molecule NN 1769 1779 expression expression NN 1780 1782 on on IN 1783 1789 HUVECs HUVEC NNP 1789 1790 , , , 1791 1798 whereas whereas IN 1799 1806 aspirin aspirin NN 1807 1810 had have VBD 1811 1813 an an DT 1814 1824 inhibitory inhibitory JJ 1825 1831 effect effect NN 1831 1832 . . . 1833 1838 These these DT 1839 1851 observations observation NNS 1852 1862 correlated correlate VBD 1863 1867 with with IN 1868 1871 the the DT 1872 1882 modulation modulation NN 1883 1885 of of IN 1886 1895 NF-kappaB NF-kappaB NNP 1896 1904 activity activity NN 1905 1907 in in IN 1908 1910 EC EC NNP 1910 1911 . . . 1912 1915 All all DT 1916 1922 agents agent NNS 1923 1929 tested test VBN 1930 1937 induced induce VBD 1938 1948 expression expression NN 1949 1951 of of IN 1952 1957 Hsp60 Hsp60 NNP 1958 1959 6 6 CD 1960 1962 hr hr NN 1963 1968 after after IN 1969 1980 application application NN 1980 1981 . . . 1982 1984 In in IN 1985 1993 addition addition NN 1993 1994 , , , 1995 2002 aspirin aspirin NN 2003 2006 and and CC 2007 2019 indomethacin indomethacin NN 2019 2020 , , , 2021 2024 but but CC 2025 2028 not not RB 2029 2032 CyA CyA NNP 2032 2033 , , , 2034 2041 induced induce VBD 2042 2047 Hsp70 hsp70 NN 2048 2058 expression expression NN 2059 2061 in in IN 2062 2068 HUVECs huvec NNS 2069 2073 that that WDT 2074 2084 correlated correlate VBD 2085 2089 with with IN 2090 2099 induction induction NN 2100 2102 of of IN 2103 2108 HSF-1 hsf-1 NN 2109 2117 activity activity NN 2117 2118 . . . 2119 2129 CONCLUSION conclusion NN 2129 2130 : : : 2131 2134 Our our PRP$ 2135 2142 results result NNS 2143 2147 show show VBP 2148 2152 that that IN 2153 2156 the the DT 2157 2163 tested test VBN 2164 2170 agents agent NNS 2171 2172 ( ( ( 2172 2178 except except IN 2179 2191 indomethacin indomethacin NN 2191 2192 ) ) ) 2193 2196 are be VBP 2197 2207 inhibitors inhibitor NNS 2208 2210 of of IN 2211 2214 the the DT 2215 2216 T t NN 2217 2230 cell-mediated cell-mediated JJ 2231 2237 immune immune JJ 2238 2246 response response NN 2246 2247 , , , 2248 2250 as as IN 2251 2259 expected expect VBN 2259 2260 , , , 2261 2265 that that IN 2266 2273 aspirin aspirin NN 2274 2276 is be VBZ 2277 2279 an an DT 2280 2289 effective effective JJ 2290 2300 suppressor suppressor NN 2301 2303 of of IN 2304 2312 adhesion adhesion NN 2313 2321 molecule molecule NN 2322 2332 expression expression NN 2332 2333 , , , 2334 2337 and and CC 2338 2342 that that IN 2343 2346 all all DT 2347 2352 three three CD 2353 2359 agents agent NNS 2360 2363 can can MD 2364 2370 induce induce VB 2371 2376 Hsp60 hsp60 NN 2377 2379 in in IN 2380 2386 HUVECs HUVEC NNP 2386 2387 . . . 2388 2393 These these DT 2394 2398 data datum NNS 2399 2406 provide provide VBP 2407 2410 the the DT 2411 2420 molecular molecular JJ 2421 2426 basis basis NN 2427 2430 for for IN 2431 2434 the the DT 2435 2441 notion notion NN 2442 2446 that that IN 2447 2448 ( ( ( 2448 2449 1 1 LS 2449 2450 ) ) ) 2451 2455 part part NN 2456 2458 of of IN 2459 2462 the the DT 2463 2479 anti-atherogenic anti-atherogenic JJ 2480 2486 effect effect NN 2487 2489 of of IN 2490 2497 aspirin aspirin NN 2498 2501 may may MD 2502 2504 be be VB 2505 2508 due due JJ 2509 2511 to to TO 2512 2515 the the DT 2516 2526 prevention prevention NN 2527 2529 of of IN 2530 2533 the the DT 2534 2542 adhesion adhesion NN 2543 2545 of of IN 2546 2556 sensitized sensitize VBN 2557 2558 T t NN 2559 2564 cells cell NNS 2565 2567 to to TO 2568 2576 stressed stressed JJ 2577 2579 EC EC NNP 2579 2580 ; ; : 2581 2582 ( ( ( 2582 2583 2 2 LS 2583 2584 ) ) ) 2585 2589 that that IN 2590 2594 part part NN 2595 2597 of of IN 2598 2601 the the DT 2602 2627 atherosclerosis-promoting atherosclerosis-promoting JJ 2628 2634 effect effect NN 2635 2637 of of IN 2638 2641 CyA CyA NNP 2642 2645 may may MD 2646 2648 be be VB 2649 2652 due due JJ 2653 2655 to to TO 2656 2659 its its PRP$ 2660 2669 potential potential NN 2670 2672 as as IN 2673 2675 an an DT 2676 2683 inducer inducer NN 2684 2686 of of IN 2687 2692 Hsp60 Hsp60 NNP 2693 2703 expression expression NN 2704 2707 and and CC 2708 2711 its its PRP$ 2712 2721 inability inability NN 2722 2724 to to TO 2725 2738 down-regulate down-regulate VB 2739 2747 adhesion adhesion NN 2748 2756 molecule molecule NN 2757 2767 expression expression NN 2768 2770 on on IN 2771 2773 EC EC NNP 2773 2774 ; ; : 2775 2778 and and CC 2779 2780 ( ( ( 2780 2781 3 3 CD 2781 2782 ) ) ) 2783 2787 that that IN 2788 2803 down-regulation down-regulation NN 2804 2806 of of IN 2807 2812 MCP-1 mcp-1 NN 2813 2823 expression expression NN 2824 2826 by by IN 2827 2834 aspirin aspirin NN 2835 2838 may may MD 2839 2845 result result VB 2846 2848 in in IN 2849 2858 decreased decrease VBN 2859 2870 recruitment recruitment NN 2871 2873 of of IN 2874 2883 monocytes monocyte NNS 2884 2888 into into IN 2889 2892 the the DT 2893 2901 arterial arterial JJ 2902 2908 intima intima NN 2909 2916 beneath beneath NN 2917 2925 stressed stress VBD 2926 2928 EC EC NNP 2928 2929 . . .