0 12 G(Anh)MTetra G(Anh)MTetra NNP 12 13 , , , 14 15 a a DT 16 23 natural natural JJ 24 33 bacterial bacterial JJ 34 38 cell cell NN 39 43 wall wall NN 44 53 breakdown breakdown NN 54 61 product product NN 61 62 , , , 63 70 induces induce VBZ 71 84 interleukin-1 interleukin-1 NN 85 89 beta beta NN 90 93 and and CC 94 107 interleukin-6 interleukin-6 NN 108 118 expression expression NN 119 121 in in IN 122 127 human human JJ 128 137 monocytes monocyte NNS 137 138 . . . 139 140 A a DT 141 146 study study NN 147 149 of of IN 150 153 the the DT 154 163 molecular molecular JJ 164 174 mechanisms mechanism NNS 175 183 involved involve VBN 184 186 in in IN 187 199 inflammatory inflammatory JJ 200 208 cytokine cytokine NN 209 219 expression expression NN 220 221 [ [ ( 221 230 published publish VBN 231 238 erratum erratum NN 239 246 appears appear VBZ 247 249 in in IN 250 251 J J NNP 252 256 Biol Biol NNP 257 261 Chem Chem NNP 262 266 1994 1994 CD 267 270 Jun Jun NNP 271 287 17;269(24):16983 17;269(24):16983 CD 287 288 ] ] ) 290 292 It it PRP 293 295 is be VBZ 296 304 believed believe VBN 305 309 that that IN 310 319 induction induction NN 320 322 of of IN 323 331 cytokine cytokine NN 332 342 expression expression NN 343 345 by by IN 346 355 bacterial bacterial JJ 356 360 cell cell NN 361 365 wall wall NN 366 376 components component NNS 377 382 plays play VBZ 383 384 a a DT 385 389 role role NN 390 392 in in IN 393 396 the the DT 397 408 development development NN 409 412 and and CC 413 419 course course NN 420 422 of of IN 423 429 sepsis sepsis NN 429 430 . . . 431 438 However however RB 438 439 , , , 440 444 most most JJS 445 454 attention attention NN 455 458 has have VBZ 459 463 been be VBN 464 471 focused focus VBN 472 474 on on IN 475 493 lipopolysaccharide lipopolysaccharide NN 494 495 ( ( ( 495 498 LPS LPS NNP 498 499 ) ) ) 499 500 . . . 501 503 We we PRP 504 511 studied study VBD 512 515 the the DT 516 523 ability ability NN 524 526 of of IN 527 587 N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D- n-acetylglucosaminyl-1,6-anhydro-n-acetylmuramyl-l-alanyl-d- NN 588 626 isoglutamyl-m-diaminopimelyl-D-alanine isoglutamyl-m-diaminopimelyl-d-alanine NN 627 628 ( ( ( 628 641 G(Anh)MTetra) G(Anh)MTetra) NNP 641 642 , , , 643 644 a a DT 645 654 naturally naturally RB 655 664 occurring occur VBG 665 674 breakdown breakdown NN 675 682 product product NN 683 685 of of IN 686 699 peptidoglycan peptidoglycan NN 700 704 that that WDT 705 707 is be VBZ 708 716 produced produce VBN 717 719 by by IN 720 727 soluble soluble JJ 728 733 lytic lytic JJ 734 750 transglycosylase transglycosylase NN 751 753 of of IN 754 765 Escherichia escherichia FW 766 770 coli coli FW 770 771 , , , 772 774 to to TO 775 781 induce induce VB 782 790 cytokine cytokine NN 791 801 expression expression NN 802 804 in in IN 805 810 human human JJ 811 820 monocytes monocyte NNS 820 821 . . . 822 834 G(Anh)MTetra G(Anh)MTetra NNP 835 838 was be VBD 839 844 found find VBN 845 847 to to TO 848 856 strongly strongly RB 857 863 induce induce VB 864 875 interleukin interleukin NN 876 877 ( ( ( 877 882 IL)-1 il)-1 NN 883 887 beta beta NN 888 891 and and CC 892 896 IL-6 IL-6 NNP 897 901 mRNA mrna NN 902 912 expression expression NN 913 918 after after IN 919 920 2 2 CD 921 922 h h NN 923 926 and and CC 927 931 IL-1 il-1 NN 932 936 beta beta NN 937 940 and and CC 941 945 IL-6 il-6 NN 946 953 protein protein NN 954 963 secretion secretion NN 964 969 after after IN 970 972 48 48 CD 973 974 h h NN 975 977 of of IN 978 988 activation activation NN 988 989 . . . 990 993 The the DT 994 1002 increase increase NN 1003 1005 in in IN 1006 1010 mRNA mrna NN 1011 1023 accumulation accumulation NN 1024 1027 was be VBD 1028 1030 at at IN 1031 1036 least least JJS 1037 1043 partly partly RB 1044 1047 due due JJ 1048 1050 to to TO 1051 1053 an an DT 1054 1062 increase increase NN 1063 1065 in in IN 1066 1069 the the DT 1070 1083 transcription transcription NN 1084 1089 rates rate NNS 1090 1092 of of IN 1093 1096 the the DT 1097 1107 respective respective JJ 1108 1113 genes gene NNS 1114 1117 and and CC 1118 1121 was be VBD 1122 1133 accompanied accompany VBN 1134 1136 by by IN 1137 1138 a a DT 1139 1145 strong strong JJ 1146 1155 induction induction NN 1156 1158 of of IN 1159 1166 nuclear nuclear JJ 1167 1179 factor-kappa factor-kappa NN 1180 1181 B b NN 1182 1185 and and CC 1186 1195 activator activator NN 1196 1205 protein-1 protein-1 NN 1206 1219 transcription transcription NN 1220 1226 factor factor NN 1227 1237 expression expression NN 1237 1238 . . . 1239 1250 Experiments experiment NNS 1251 1256 using use VBG 1257 1267 inhibitors inhibitor NNS 1268 1270 of of IN 1271 1278 protein protein NN 1279 1285 kinase kinase NNP 1286 1287 C C NNP 1287 1288 , , , 1289 1296 protein protein NN 1297 1303 kinase kinase NNP 1304 1305 A A NNP 1305 1306 , , , 1307 1310 and and CC 1311 1319 tyrosine tyrosine NN 1320 1336 kinase-dependent kinase-dependent JJ 1337 1345 pathways pathway NNS 1346 1354 revealed reveal VBD 1355 1359 that that IN 1360 1380 G(Anh)MTetra-induced g(anh)mtetra-induced JJ 1381 1385 IL-1 il-1 NN 1386 1390 beta beta NN 1391 1394 and and CC 1395 1399 IL-6 IL-6 NNP 1400 1404 mRNA mrna NN 1405 1415 expression expression NN 1416 1424 involves involve VBZ 1425 1435 activation activation NN 1436 1438 of of IN 1439 1441 an an DT 1442 1456 H7-inhibitable h7-inhibitable JJ 1457 1464 pathway pathway NN 1464 1465 . . . 1466 1468 By by IN 1469 1474 using use VBG 1475 1478 the the DT 1479 1486 protein protein NN 1487 1496 synthesis synthesis NN 1497 1506 inhibitor inhibitor NN 1507 1520 cycloheximide cycloheximide NN 1520 1521 , , , 1522 1524 it it PRP 1525 1528 was be VBD 1529 1534 shown show VBN 1535 1539 that that IN 1540 1560 G(Anh)MTetra-induced g(anh)mtetra-induced JJ 1561 1565 IL-6 IL-6 NNP 1566 1570 mRNA mRNA NNP 1571 1581 expression expression NN 1582 1589 depends depend VBZ 1590 1592 on on IN 1593 1596 the the DT 1597 1606 synthesis synthesis NN 1607 1609 of of IN 1610 1613 new new JJ 1614 1621 protein protein NN 1621 1622 , , , 1623 1630 whereas whereas IN 1631 1651 G(Anh)MTetra-induced g(anh)mtetra-induced JJ 1652 1656 IL-1 il-1 NN 1657 1661 beta beta NN 1662 1666 mRNA mrna NN 1667 1679 accumulation accumulation NN 1680 1684 does do VBZ 1685 1688 not not RB 1688 1689 . . . 1690 1694 When when WRB 1695 1704 responses response NNS 1705 1707 to to TO 1708 1720 G(Anh)MTetra G(Anh)MTetra NNP 1721 1725 were be VBD 1726 1734 compared compare VBN 1735 1739 with with IN 1740 1745 those those DT 1746 1748 to to TO 1749 1752 LPS LPS NNP 1753 1756 and and CC 1757 1773 muramyldipeptide muramyldipeptide NN 1774 1775 ( ( ( 1775 1778 MDP MDP NNP 1778 1779 ) ) ) 1779 1780 , , , 1781 1783 it it PRP 1784 1787 was be VBD 1788 1793 found find VBN 1794 1798 that that IN 1799 1802 the the DT 1803 1810 optimal optimal JJ 1811 1819 response response NN 1820 1822 to to TO 1823 1835 G(Anh)MTetra G(Anh)MTetra NNP 1836 1845 induction induction NN 1846 1849 was be VBD 1850 1857 similar similar JJ 1858 1860 to to TO 1861 1865 that that DT 1866 1868 of of IN 1869 1872 LPS LPS NNP 1873 1876 but but CC 1877 1890 significantly significantly RB 1891 1897 higher high JJR 1898 1902 than than IN 1903 1906 the the DT 1907 1915 response response NN 1916 1918 to to TO 1919 1922 MDP MDP NNP 1922 1923 . . . 1924 1935 Furthermore furthermore RB 1935 1936 , , , 1937 1944 maximal maximal JJ 1945 1965 G(Anh)MTetra-induced g(anh)mtetra-induced JJ 1966 1970 IL-1 il-1 NN 1971 1975 beta beta NN 1976 1979 and and CC 1980 1984 IL-6 IL-6 NNP 1985 1989 mRNA mrna NN 1990 2000 expression expression NN 2001 2006 could could MD 2007 2009 be be VB 2010 2018 enhanced enhance VBN 2019 2021 by by IN 2022 2036 co-stimulation co-stimulation NN 2037 2041 with with IN 2042 2045 LPS LPS NNP 2046 2048 or or CC 2049 2052 MDP MDP NNP 2052 2053 , , , 2054 2064 suggesting suggest VBG 2065 2069 that that IN 2070 2079 different different JJ 2080 2089 receptors receptor NNS 2090 2096 and/or and/or CC 2097 2109 transduction transduction NN 2110 2118 pathways pathway NNS 2119 2123 were be VBD 2124 2132 involved involve VBN 2132 2133 . . . 2134 2139 These these DT 2140 2147 results result NNS 2148 2156 indicate indicate VBP 2157 2161 that that IN 2162 2174 G(Anh)MTetra G(Anh)MTetra NNP 2175 2182 induces induce VBZ 2183 2187 IL-1 il-1 NN 2188 2192 beta beta NN 2193 2196 and and CC 2197 2201 IL-6 il-6 NN 2202 2212 expression expression NN 2213 2215 in in IN 2216 2221 human human JJ 2222 2231 monocytes monocyte NNS 2232 2242 suggesting suggest VBG 2243 2244 a a DT 2245 2253 possible possible JJ 2254 2258 role role NN 2259 2262 for for IN 2263 2275 G(Anh)MTetra G(Anh)MTetra NNP 2276 2278 in in IN 2279 2282 the the DT 2283 2290 release release NN 2291 2293 of of IN 2294 2303 cytokines cytokine NNS 2304 2310 during during IN 2311 2317 sepsis sepsis NN 2317 2318 . . .