0 10 Surfactant Surfactant NNP 11 21 suppresses suppress VBZ 22 30 NF-kappa NF-kappa NNP 31 32 B B NNP 33 43 activation activation NN 44 46 in in IN 47 52 human human JJ 53 62 monocytic monocytic JJ 63 68 cells cell NNS 68 69 . . . 71 73 In in IN 74 82 addition addition NN 83 85 to to TO 86 97 biophysical biophysical JJ 98 108 properties property NNS 108 109 , , , 110 119 pulmonary pulmonary JJ 120 130 surfactant surfactant NN 131 134 has have VBZ 135 151 immunomodulatory immunomodulatory JJ 152 160 activity activity NN 160 161 . . . 162 164 We we PRP 165 175 previously previously RB 176 188 demonstrated demonstrate VBD 189 193 that that IN 194 198 both both CC 199 208 synthetic synthetic JJ 209 210 ( ( ( 210 217 Exosurf Exosurf NNP 217 218 ) ) ) 219 222 and and CC 223 231 modified modify VBN 232 239 natural natural JJ 240 250 surfactant surfactant NN 251 252 ( ( ( 252 260 Survanta Survanta NNP 260 261 ) ) ) 262 275 downregulated downregulate VBD 276 296 endotoxin-stimulated endotoxin-stimulated JJ 297 309 inflammatory inflammatory JJ 310 318 cytokine cytokine NN 319 323 mRNA mrna NN 324 330 levels level NNS 331 334 and and CC 335 342 protein protein NN 343 351 products product NNS 352 353 ( ( ( 353 358 tumor tumor NN 359 367 necrosis necrosis NN 368 380 factor-alpha factor-alpha NN 381 382 [ [ ( 382 385 TNF TNF NNP 385 386 ] ] ) 386 387 , , , 388 406 interleukin-1-beta interleukin-1-beta NN 407 408 [ [ ( 408 412 IL-1 IL-1 NNP 412 413 ] ] ) 413 414 , , , 415 428 interleukin-6 interleukin-6 NN 429 430 [ [ ( 430 434 IL-6 IL-6 NNP 434 435 ] ] ) 435 436 ) ) ) 437 439 in in IN 440 445 human human JJ 446 454 alveolar alveolar JJ 455 466 macrophages macrophage NNS 466 467 . . . 468 470 In in IN 471 475 this this DT 476 481 study study NN 481 482 , , , 483 485 we we PRP 486 492 report report VBP 493 497 that that IN 498 502 both both CC 503 510 Exosurf Exosurf NNP 511 514 and and CC 515 523 Survanta Survanta NNP 524 532 suppress suppress VBP 533 536 TNF TNF NNP 537 541 mRNA mRNA NNP 542 545 and and CC 546 555 secretion secretion NN 556 557 ( ( ( 557 559 85 85 CD 560 563 +/- +/- SYM 564 565 4 4 CD 565 566 % % NN 567 571 mean mean JJ 572 579 percent percent NN 580 590 inhibition inhibition NN 591 594 +/- +/- CC 595 598 SEM SEM NNP 599 601 by by IN 602 609 Exosurf Exosurf NNP 609 610 ; ; : 611 613 71 71 CD 614 617 +/- +/- CC 618 619 6 6 CD 619 620 % % NN 621 623 by by IN 624 632 Survanta Survanta NNP 632 633 ) ) ) 634 636 by by IN 637 657 endotoxin-stimulated endotoxin-stimulated JJ 658 663 THP-1 thp-1 NN 663 664 , , , 665 666 a a DT 667 672 human human JJ 673 682 monocytic monocytic JJ 683 687 cell cell NN 688 692 line line NN 692 693 . . . 694 701 Because because IN 702 712 surfactant surfactant NN 713 726 downregulated downregulate VBD 727 739 inflammatory inflammatory JJ 740 748 cytokine cytokine NN 749 759 production production NN 760 769 similarly similarly RB 770 772 in in IN 773 777 both both CC 778 784 normal normal JJ 785 790 human human JJ 791 799 alveolar alveolar JJ 800 811 macrophages macrophage NNS 812 815 and and CC 816 819 the the DT 820 825 THP-1 thp-1 NN 826 830 cell cell NN 831 835 line line NN 835 836 , , , 837 839 we we PRP 840 844 used use VBD 845 849 this this DT 850 854 cell cell NN 855 859 line line NN 860 862 to to TO 863 874 investigate investigate VB 875 882 whether whether IN 883 893 surfactant surfactant JJ 894 902 affected affect VBN 903 918 transcriptional transcriptional JJ 919 929 mechanisms mechanism NNS 929 930 . . . 931 943 Specifically specifically RB 943 944 , , , 945 947 we we PRP 948 956 examined examine VBD 957 964 nuclear nuclear JJ 965 977 factor-kappa factor-kappa NN 978 979 B B NNP 980 981 ( ( ( 981 989 NF-kappa NF-kappa NNP 990 991 B B NNP 991 992 ) ) ) 993 1003 activation activation NN 1004 1011 because because IN 1012 1014 it it PRP 1015 1017 is be VBZ 1018 1025 crucial crucial JJ 1026 1028 in in IN 1029 1044 transcriptional transcriptional JJ 1045 1055 regulation regulation NN 1056 1058 of of IN 1059 1063 many many JJ 1064 1076 inflammatory inflammatory JJ 1077 1085 cytokine cytokine NN 1086 1091 genes gene NNS 1092 1101 including include VBG 1102 1105 TNF TNF NNP 1105 1106 , , , 1107 1111 IL-1 IL-1 NNP 1111 1112 , , , 1113 1116 and and CC 1117 1121 IL-6 IL-6 NNP 1121 1122 . . . 1123 1138 Electrophoretic electrophoretic JJ 1139 1147 mobility mobility NN 1148 1153 shift shift NN 1154 1160 assays assay NNS 1161 1167 showed show VBD 1168 1172 that that IN 1173 1177 both both DT 1178 1189 surfactants surfactant NNS 1190 1199 decreased decrease VBD 1200 1210 activation activation NN 1211 1213 of of IN 1214 1222 NF-kappa NF-kappa NNP 1223 1225 B. B. NNP 1226 1229 The the DT 1230 1238 presence presence NN 1239 1241 of of IN 1242 1246 both both CC 1247 1250 p65 p65 NN 1251 1254 and and CC 1255 1258 p50 p50 NN 1259 1267 NF-kappa NF-kappa NNP 1268 1269 B B NNP 1270 1280 components component NNS 1281 1283 in in IN 1284 1297 LPS-activated lps-activated JJ 1298 1303 THP-1 thp-1 NN 1304 1309 cells cell NNS 1310 1313 was be VBD 1314 1323 confirmed confirm VBN 1324 1326 by by IN 1327 1335 specific specific JJ 1336 1344 antibody antibody NN 1345 1354 induction induction NN 1355 1357 of of IN 1358 1369 supershifts supershift NNS 1370 1372 in in IN 1373 1381 mobility mobility NN 1382 1388 assays assay NNS 1388 1389 . . . 1390 1395 These these DT 1396 1403 results result NNS 1404 1407 are be VBP 1408 1411 the the DT 1412 1417 first first JJ 1418 1420 to to TO 1421 1428 suggest suggest VB 1429 1433 that that IN 1434 1444 surfactant surfactant NN 1444 1446 ’s 's POS 1447 1458 suppressive suppressive JJ 1459 1466 effects effect NNS 1467 1469 on on IN 1470 1482 inflammatory inflammatory JJ 1483 1491 cytokine cytokine NN 1492 1502 production production NN 1503 1506 may may MD 1507 1514 involve involve VB 1515 1530 transcriptional transcriptional JJ 1531 1541 regulation regulation NN 1542 1549 through through IN 1550 1560 inhibition inhibition NN 1561 1563 of of IN 1564 1572 NF-kappa NF-kappa NNP 1573 1574 B B NNP 1575 1585 activation activation NN 1585 1586 . . .